KR20080098043A - Indolopyridines as eg5 kinesin modulators - Google Patents

Abstract

Compounds of a certain formula (I), in which R1, R2, R3, R4, R5 and R6 have the meanings indicated in the description, are effective compounds with anti-proliferative and/or apoptosis inducing activity.

Description

INDOLOPYRIDINES AS EG5 KINESIN MODULATORS as EV5 Kinesine Modulator

The present invention relates to indolopyridine derivatives that can be used in the pharmaceutical industry for the manufacture of pharmaceutical compositions.

Hotha et al., Angew. Chem. 2003, 115, 2481-2484, describes indolopyridine compound HR22C16 as an inhibitor of cell division by targeting of Eg5.

EP357122 contains especially indolopyridine, benzofuranopyridine and benzothienopyridine derivatives as cell division inhibitory compounds.

International applications WO9632003 and WO0228865 describe indolopyridine derivatives having PDE inhibitory activity.

International application WO 2004/004652 specifically describes trans-10- (3-hydroxy-phenyl) -2-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b]. Fluorene-1,3-dione is described as a crystallized complex with kinesin spindle protein (KSP).

US application US 2005/0004156 describes indolopyridine derivatives, in particular monastroline derivatives, as Eg5 inhibitors.

Bioorg. Med. Chem. 13 (2005) 6094-6111 describes tetrahydro-ß-carboline as an Eg5 inhibitor.

J. Org. Chem., Vol. 59, no. 6, 1994, p. 1583-1585 and Chem. Pharm. Bull., Vol. 42, no. 10, 1994, p. 2108-2112 describes the reaction of tetrahydro-ß-carboline-3-carboxylic acids with isocyanates and isothiocyanates.

J. Med. Chem., Vol. 46, no. 21, 2003, p. 4525-4532 describe indolopyridine derivatives having PDE5 inhibitory activity.

International application WO 2005/089752 describes tetracyclic carboline derivatives as inhibitors of VEGF production.

DE19744257 describes 2H-pyrrolo [3,4-c] beta-carboline as a tyrosine kinase inhibitor that can be used for the treatment of malignant diseases.

It has now been found that the indolopyridine derivatives described in more detail below differ from the compounds of the prior art by unexpected structural features and have surprising and particularly advantageous properties.

Thus, for example, the compounds according to the invention can act as inhibitors of Eg5 kinesin.

More specifically, it was unexpectedly found that the derivatives are potent and very effective inhibitors of cell (hyper) proliferation and / or cell-cycle specific inducers of apoptosis in cancer cells. Therefore, these compounds may be particularly useful for treating (hyper) proliferative diseases and / or disorders, particularly cancer, which are responsive to the induction of apoptosis. By having a cell-cycle specific mode of action, the derivative will have a higher therapeutic index compared to standard chemotherapy drugs that target basic cell molecules such as DNA.

Thus, for example, the compounds according to the invention are expected to be useful in targeted cancer therapy.

Thus, in a first aspect (Side A), the present invention relates to compounds of formula (I) and salts, stereoisomers and salts of stereoisomers of these compounds:

Where

R1 is 1-4C-alkyl, 3-7C-cycloalkyl, 2-4C-alkenyl, 2-4C-alkynyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C substituted with R11 -Alkyl,

R11 is -N (R111) R112, or halogen,

R111 is hydrogen, 1-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C -Alkyl, 1-4C-alkoxy-2-4C-alkyl, 1N- (1-4C-alkyl) -pyrazolyl, 1N- (H) -pyrazolyl, isoxazolyl, or fully or partially fluorine-substituted 1-4C-alkyl,

R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, or 3-7C-cycloalkyl-1-4C-alkyl,

R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thio-morpholine-4 -Yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin- 1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazole-1 -Yl, triazol-1-yl, or tetrazol-1-yl,

R113 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkylcarbonyl, amidino, or fully or partially fluorine-substituted 1-4C-alkyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and 1-4C-alkyl,

R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl,

R 3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy,

R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl,

R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy -2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy,

R 6 is hydrogen, 1-4C-alkyl or halogen.

Further, in a second aspect (side B), which is one embodiment of side A, the invention

R 1 is 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C-alkyl substituted with R 11,

R11 is -N (R111) R112, or halogen,

R111 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl Or fully or partially fluorine-substituted 1-4C-alkyl,

R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, or 3-7C-cycloalkyl-1-4C-alkyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4- Il, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1 -Yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazol-1-yl, or tetrazol-1-yl,

R113 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkylcarbonyl, amidino, or fully or partially fluorine-substituted 1-4C-alkyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and 1-4C-alkyl,

R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl,

R3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy,

R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl,

R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy,

R 6 is hydrogen, 1-4C-alkyl or halogen

It relates to compounds of formula (I) and salts, stereoisomers and salts of stereoisomers of these compounds.

In addition, in a third aspect (side C), which is also an embodiment of side A,

R 1 is 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl,

R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4- 1, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl ,

R113 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl,

R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl,

R3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy,

R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl,

R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy,

R 6 is hydrogen, 1-4C-alkyl or halogen

It relates to compounds of formula (I) and salts, stereoisomers and salts of stereoisomers of these compounds.

As used herein, "alkyl", alone or as part of another group, means both branched and straight chain saturated aliphatic hydrocarbon groups having a specified number of carbon atoms, for example:

1-4C-alkyl is a straight or branched alkyl radical of 1 to 4 carbon atoms. Examples are butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methyl radicals, of which propyl, isopropyl, in particular ethyl and methyl, are worth mentioning more.

2-7C-alkyl is a straight or branched alkyl radical of 2 to 7 carbon atoms. Examples are heptyl, isoheptyl (5-methylhexyl), hexyl, isohexyl (4-methylpentyl), neohexyl (3,3-dimethylbutyl), pentyl, isopentyl (3-methylbutyl), neopentyl ( 2,2-dimethylpropyl), butyl, isobutyl, sec-butyl, tert-butyl, isopropyl, especially propyl and ethyl radicals.

2-4C-alkyl is a straight or branched alkyl radical of 2 to 4 carbon atoms. Examples are butyl, isobutyl, sec-butyl, tert-butyl, isopropyl, especially propyl and ethyl radicals.

Halogen within the meaning of the present invention is iodine or in particular bromine, chlorine or fluorine.

1-4C alkoxy refers to radicals containing straight or branched alkyl radicals having from 1 to 4 carbon atoms in addition to oxygen atoms. Examples that may be mentioned are butoxy, isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy, ethoxy and methoxy radicals, among which propoxy, isopropoxy, in particular ethoxy and Methoxy deserves further mention.

The term "cycloalkyl", alone or as part of another group, means a monocyclic saturated aliphatic hydrocarbon group having a specified number of ring carbon atoms, for example:

3-7C-cycloalkyl represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, of which cyclopropyl, cyclobutyl and cyclopentyl may be mentioned in particular.

3-7C-cycloalkyl-1-4C-alkyl denotes one of the aforementioned 1-4C-alkyl radicals substituted with one of the aforementioned 3-7C-cycloalkyl radicals. Examples that may be mentioned are 3-7C-cycloalkylmethyl radicals, for example cyclopropylmethyl, cyclobutylmethyl or cyclopentylmethyl, of which cyclopropylmethyl may in particular be mentioned.

2-4C-alkenyl is a straight or branched alkenyl radical having 2 to 4 carbon atoms. Examples are 2-butenyl, 3-butenyl (holy allyl), 1-propenyl, 2-propenyl (allyl) and ethenyl (vinyl) radicals.

2-4C-alkynyl is a straight or branched alkynyl radical having 2 to 4 carbon atoms. Examples are 2-butynyl, 3-butynyl (homopropargyl), 1-propynyl, 2-propynyl (propargyl), 1-methyl-2-propynyl (1-methyl-propargyl ) And ethynyl radicals.

2-4C-alkoxy refers to radicals containing straight or branched alkyl radicals having from 2 to 4 carbon atoms in addition to oxygen atoms. Examples that may be mentioned are butoxy, isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy, in particular ethoxy radicals.

1-4C alkoxy-2-4C alkoxy refers to one of the aforementioned 2-4C alkoxy radicals substituted with one of the aforementioned 1-4C alkoxy radicals. Examples that may be mentioned are 2-methoxyethoxy, 2-ethoxyethoxy and 2-isopropoxyethoxy radicals.

Hydroxy-2-4C alkoxy refers to one of the aforementioned 2-4C alkoxy radicals substituted with hydroxyl radicals. Examples that may be mentioned are 2-hydroxyethoxy and 3-hydroxypropoxy radicals.

3-7C-cycloalkoxy represents cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy or cycloheptyloxy, of which cyclopropyloxy, cyclobutyloxy and cyclopentyloxy may be mentioned in particular.

3-7C-cycloalkyl-1-4C-alkoxy refers to one of the aforementioned 1-4C-alkoxy radicals substituted with one of the aforementioned 3-7C-cycloalkyl radicals. Examples that may be mentioned are 3-7C-cycloalkylmethoxy radicals, for example cyclopropylmethoxy, cyclobutylmethoxy or cyclopentylmethoxy, of which cyclopropylmethoxy may be mentioned in particular.

Fully or predominantly fluorine-substituted 1-4C-alkoxy is, for example, 2,2,3,3,3-pentafluoropropoxy, perfluoroethoxy, 1,2,2-trifluoro Methoxy, in particular 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, trifluoromethoxy and difluoromethoxy radicals, of which trifluoromethoxy and difluoro Lomethoxy radicals are preferred. "Predominantly" in this context means that at least half of the hydrogen atoms of the 1-4C-alkoxy group are substituted with fluorine atoms.

Phenyl-1-4C-alkoxy represents one of the aforementioned 1-4C-alkoxy radicals substituted with phenyl radicals. Examples that may be mentioned are phenoxy and benzyloxy radicals.

1-4C-alkylcarbonyl is a carbonyl group to which one of the aforementioned 1-4C-alkyl radicals is bound. An example is the acetyl radical (CH ₃ CO-).

1N- (1-4C-alkyl) -pyrazolyl or 1N- (H) -pyrazolyl are pyrazolyl radicals, each in particular 1-methyl, in which the ring nitrogen atom in the 1-position is replaced by 1-4C-alkyl or hydrogen, respectively -Pyrazol-5-yl or 1-methyl-pyrazol-3-yl radical.

Fully or partially fluorine-substituted 1-4C-alkyl, for example 2,2,3,3,3-pentafluoropropyl, perfluoroethyl, 1,2,2-trifluoroethyl, 1 , 1,2,2-tetrafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethyl, difluoromethyl, monofluoromethyl, 2-fluoroethyl and 2,2-difluoro Mention may be made of roethyl radicals, in particular 2,2,2-trifluoroethyl, 2,2-difluoroethyl and 2-fluoroethyl radicals.

Het is optionally substituted with 1 or 2 substituents independently selected from 1-4C-alkyl and fluorine, and piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo- Thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- ( R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridine-1 -Yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazol-1-yl, or tetrazol-1-yl, wherein

R21 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkylcarbonyl, amidino, or fully or partially fluorine-substituted 1-4C-alkyl,

Especially

R21 is hydrogen, 1-3C-alkyl, cyclopropyl, cyclopropylmethyl, 1-2C-alkylcarbonyl, or partially fluorine-substituted 1-3C-alkyl (eg 2-fluoroethyl, 2,2 , 2-trifluoroethyl, or especially 2,2-difluoroethyl).

In a first embodiment, Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl or azetidin-1-yl.

In a second embodiment, Het is 4N- (R113) -piperazin-1-yl, wherein

R21 is hydrogen, methyl, ethyl, isopropyl, cyclopropyl, cyclopropylmethyl, 1-2C-alkylcarbonyl, 2-fluoroethyl, 2,2,2-trifluoroethyl or 2,2-difluoro Ethyl;

For example 4-methyl-piperazin-1-yl or 4-acetyl-piperazin-1-yl.

In a third embodiment, Het is optionally substituted with one or two substituents independently selected from methyl and fluorine and piperidin-1-yl, pyrrolidin-1-yl, azetidin-1-yl or homopy Ferridin-1-yl, for example piperidin-1-yl, pyrrolidin-1-yl or azetidin-1-yl, or 4-methyl-piperidin-1-yl, 4-fluoro -Piperidin-1-yl, 4,4-difluoro-piperidin-1-yl, (S) -3-fluoro-pyrrolidin-1-yl, (R) -3-fluoro -Pyrrolidin-1-yl, 3,3-difluoro-pyrrolidin-1-yl, 3-fluoro-azetidin-1-yl or 3,3-difluoro-azetidin-1- It's work.

In a fourth embodiment, Het is pyrazol-1-yl, imidazol-1-yl or triazol-1-yl, in particular imidazol-1-yl.

In a fifth embodiment, Het is 2,5-dihydro-pyrrole-1-yl or 1,2,3,6-tetrahydropyridin-1-yl.

Amino-1-4C-alkyl refers to the abovementioned 1-4C-alkyl radical substituted with an amino group. Examples that may be mentioned are aminomethyl, 2-aminoethyl and 3-aminopropyl radicals.

Hydroxy-2-4C-alkyl refers to the aforementioned 2-4C-alkyl radicals substituted with hydroxyl groups. Examples that may be mentioned are 2-hydroxyethyl and 3-hydroxypropyl radicals.

1-4C-alkoxy-2-4C-alkyl refers to the aforementioned 2-4C-alkyl radicals substituted with one of the 1-4C-alkoxy radicals mentioned above. Examples that may be mentioned are 2-methoxyethyl and 3-methoxypropyl radicals.

Mono- or di-1-4C-alkylamino radicals contain one or two of the aforementioned 1-4C-alkyl radicals in addition to the nitrogen atom. Examples that may be mentioned are mono-1-4C-alkylamino radicals such as methylamino, ethylamino or isopropylamino, and di-1-4C-alkylamino radicals such as dimethylamino, diethylamino or diisopropylamino to be.

Mono- or di-1-4C-alkylamino-1-4C-alkyl represents one of the aforementioned 1-4C-alkyl groups substituted with one of the above-mentioned mono- or di-1-4C-alkylamino groups . Examples that may be mentioned are the methylamino-methyl, dimethylamino-methyl, 2-methylamino-ethyl, 2-dimethylamino-ethyl, 3-methylamino-propyl or 3-dimethylamino-propyl radicals.

4N- (R113) -piperazin-1-yl or 4N- (R113) -homopiperazin-1-yl is piperazin-1-yl or homopiperazin- substituted with R113 on a ring nitrogen atom at the 4-position, respectively; Represents a 1-day radical.

The term 2- (R11) -ethyl refers to ethyl substituted with R11 in the 2-position. The term 3- (R11) -propyl refers to a propyl substituted with R11 at the 3-position. The term 4- (R11) -butyl denotes butyl substituted in the 4-position with R11.

In general, unless otherwise stated, heterocyclic radicals include all possible isomeric forms thereof, such as positional isomers thereof. Thus, for example, the term triazol-1-yl refers to [1,2,3] triazol-1-yl, [1,3,4] triazol-1-yl and [1,2,4] triazole -1-yl, or the term isoxazolyl includes isoxazol-3-yl, isoxazol-4-yl and isoxazol-5-yl.

Optionally substituted members as described herein may be substituted at any possible position unless otherwise noted.

Unless stated otherwise, the carbocyclic radicals mentioned herein may be substituted with their substituents or parent molecular groups at any possible position.

The heterocyclic groups referred to herein may be substituted at any possible position, for example at any substitutable ring carbon or ring nitrogen atom, with their given substituents or parent molecular groups, unless stated otherwise.

Unless stated otherwise, rings containing quaternizable amino- or imino-type ring nitrogen atoms (-N =) are preferably the substituents or parent molecules mentioned on these amino- or imino-type ring nitrogen atoms May not be quaternized.

If any variable exists more than once in any member, each definition is independent.

Suitable salts (depending on the substituent) for the compounds of formula (I) according to the invention are all acid addition salts or all salts with bases. Particular mention may be made of the pharmacologically acceptable inorganic and organic acids and bases commonly used in pharmacy. On the one hand, acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, Lauric acid, malic acid, such as (-)-L-malic acid or (+)-D-malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, such as (+)-L-tartaric acid or (-)-D-tartaric acid or meso- Water-insoluble and especially water-soluble acid addition salts with tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid are suitable, and the acid is (whether monobasic acid or polybasic acid is involved) And depending on which salt is preferred) in quantitative ratios of equal moles or else for salt preparation.

In this context, as further acids which can be used in the preparation of possible salts of the compounds of the formula (I), for example, adipic acid, L-ascorbic acid, L-aspartic acid, benzenesulfonic acid, 4-acetamido-benzoic acid , (+)-Camphor acid, (+)-campo-10-sulfonic acid, caprylic acid (octanoic acid), dodecylsulfonic acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, Formic acid, galactaric acid, gentisic acid, D-glucoheptonic acid, D-glucuronic acid, glutamic acid, 2-oxo-glutaric acid, hypofuric acid, lactic acid such as D-lactic or L-lactic acid, malonic acid, Mandelic acid, such as (+)-mandelic acid or (-)-mandelic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, palmitic acid, pyroglutamic acid, such as L-pyroglutamic acid, hydroiodic acid , Cyclic acid, thiocyanic acid, 2,2-dichloroacetic acid, glycerophosphoric acid, 1-hydroxy-2-naphthoic acid, salicylic acid, 4-aminosalicylic acid, glycolic acid, oleic acid, Rutile acid, cinnamic acid, caproic acid, may be mentioned that isobutyric acid, propionic acid, capric acid, undecylenic acid and O any acid selected from the lot.

On the other hand, salts with bases (depending on the substituent) are also suitable. As examples of salts with bases, lithium, sodium, potassium, calcium, aluminum, magnesium, titanium, ammonium, meglumine or guanidinium salts are also mentioned herein, wherein the bases are salts in quantitative proportions or otherwise Used for manufacturing.

Also included are salts which are unsuitable for pharmaceutical use but which can be used, for example, in the isolation or purification of the free compound of formula (I) or a pharmaceutically acceptable salt thereof.

For example, pharmacologically unacceptable salts which can be obtained as process products during the preparation of compounds according to the invention on an industrial scale are converted to pharmacologically acceptable salts by methods known to those skilled in the art.

According to the expert's knowledge, the compounds of formula (I) and their salts according to the invention may contain various amounts of solvent, for example when isolated in crystalline form. Therefore, all solvates, in particular all hydrates of the compounds of formula (I) according to the invention as well as all solvates, especially all hydrates of salts of the compounds of formula (I) according to the invention, are included within the scope of the invention.

In one embodiment of the invention, the salt of the compound of formula (I) comprises a salt of the compound of formula (I) with hydrochloric acid (hydrochloride).

In another embodiment of the present invention, salts of compounds of formula (I) include hydrochloride, phosphate, citrate, tartrate, mesylate, tosylate and sulfate.

Substituents R2 and R3 of compounds of formula (I) may be attached to the ortho, meta or para position with respect to the bonding position to which the phenyl ring binds to the backbone. In one embodiment, R 3 is hydrogen. In a specific embodiment, R 2 and R 3 are both hydrogen.

Substituents R5 and R6 may be attached at any position of the benzene moiety of the skeleton, unless otherwise noted, and neither of R5 and R6 is attached at the 8-position of the skeleton. In one embodiment, R 5 is attached at the 5-position of the skeleton, in another embodiment, R 5 is attached at the 7-position of the skeleton, and in another embodiment R 5 is attached at the 6-position of the skeleton, in particular And R6 are each hydrogen or R6 is each fluorine. In a specific embodiment, R 5 is attached at the 6-position of the backbone. In a more specific embodiment, R 5 is attached at the 6-position of the skeleton and R 6 is hydrogen. In another embodiment, R 5 is attached at the 6-position of the skeleton and R 6 is attached at the 7-position of the skeleton and is fluorine. In another embodiment, R 5 is attached at the 6-position of the skeleton and R 6 is attached at the 5-position of the backbone and is fluorine.

Compounds of formula (I) are chiral compounds having a chiral center at least at positions 3a and 10.

The present invention includes not only substantially pure forms but also all conceivable stereoisomers, including diastereomers and enantiomers, as well as salts thereof, with any mixing ratio, including racemates.

Accordingly, the substantially pure stereoisomers of the compounds according to the invention, in particular the substantially pure stereoisomers of the following examples, are all part of the present invention and according to procedures conventional to those skilled in the art, for example, the separation of the corresponding mixture, stereochemically Obtained by the use of pure starting materials and / or by stereoselective synthesis.

Preferred are compounds of formula (I) having the same configuration as shown in formula (I *) below for positions 3a and 10:

<Formula I *>

For example, in the compounds of Formula I *, if R4 has the meaning methyl or ethyl, the coordination (according to the rules of Cahn, Ingold and Prelog) is at S and R at position 10.

For example, in the compounds of formula (I *) where R 4 has the meaning of isopropyl or cyclopropyl, the coordination (according to the rules of cannes, ingold and prelog) is R at position 3a and R at position 10.

Also of note are compounds of formula (I) having the same configuration as shown in formula (I **) for positions 3a and 10.

<Formula I **>

For example, in the compounds of formula (I **) where R 4 has the meaning methyl or ethyl, the coordination (according to the rules of cannes, ingold and prelog) is R at position 3a and R at position 10.

For example, in the compounds of formula (I **) where R 4 has the meaning of isopropyl or cyclopropyl, the coordination (according to the rules of cannes, ingold and prelogs) is R at positions 3a and S at position 10.

In addition, mention may also be made of compounds of the formula (I) which have the same configuration as shown in the formulas (I ***) or (I ****) below for positions 3a and 10.

<Formula I ***>

<Formula I ****>

For example, when R 4 in the compound of formula I *** has the meaning methyl or ethyl, the coordination (according to the rules of cannes, ingold and prelog) is R at position 3a and S at position 10.

For example, in the compounds of formula I ***, when R 4 has the meaning of isopropyl or cyclopropyl, the coordination (according to the rules of cannes, ingold and prelog) is S at position 3a and S at position 10 .

For example, when R 4 in the compound of formula I **** has the meaning methyl or ethyl, the coordination (according to the rules of cannes, ingold and prelog) is S at position 3a and S at position 10.

For example, in the compounds of formula I ****, if R4 has the meaning of isopropyl or cyclopropyl, the coordination (according to the rules of cannes, ingold and prelogs) is S at the 3a position and S at the 10 position to be.

In this regard, in another embodiment, (-)-2- (with specific optical rotation [α] ²⁰ _D = -159 ° (c = 0.5400, methanol) for positions 3a and 10 2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta Preferred are compounds of formula (I) and salts thereof having the same absolute configuration as the [b] fluorene-1,3-dione compound.

In general, enantiomerically pure compounds of the invention are prepared according to methods known in the art, for example via asymmetric synthesis, for example known methods (eg chromatographic separation or from a suitable solvent (fractionation). By the preparation and separation of suitable diastereomeric compounds / intermediates which can be separated by crystallization) or by using chiral synthons or chiral reagents; By chromatographic separation of the corresponding racemate compound on a chiral separation column; By diastereomeric salt formation of the racemate compound with an optically active acid (such as those mentioned later herein) or a base, followed by separation of the salt and release of the desired compound from the salt; Derivatization of the corresponding racemate compound with chiral adjuvant reagents, followed by diastereoisomeric separation and removal of chiral adjuvant groups; By kinetic cleavage of the racemate (eg by enzymatic cleavage); By isoselective (preferred) crystallization (or crystallization with entrainment) from the aggregate of enantiomeric crystals under suitable conditions; Or (fractional) crystallization from a suitable solvent in the presence of a chiral adjuvant.

Preferably, the enantiomerically pure compound starts from known enantiomerically pure starting compounds, by known methods (eg by chromatographic separation or crystallization), or on a corresponding chiral separation column. Obtained through the synthesis of diastereomeric intermediates that can be separated by chromatographic cleavage of racemates.

Enantiomers having the formula I * and salts thereof are preferred parts of the present invention.

In the context of the present invention, hyperproliferation and similar terms are used to describe aberrant / unregulated cell growth that is characteristic of diseases such as cancer. The hyperproliferation can be caused by single or multiple cell / molecular changes in each cell and can exhibit positive or malignant behavior for the whole organism. Inhibition of cell proliferation and similar terms are used to refer to a compound's ability to retard growth and / or kill cells in contact with the compound relative to cells not in contact with the compound. Most preferably, the inhibition of cell proliferation is 100%, which means that all cells proliferate and / or the cells undergo programmed cell death. In some preferred embodiments, the contacted cells are neoplastic cells. Neoplastic cells are defined as cells that have abnormal cell proliferation and / or are likely to metastasize to other tissues or organs. Positive neoplasms are described as overproliferation of cells that are unable to form aggressive metastatic tumors in vivo. In contrast, malignant neoplasms are described as cells with different cellular and biochemical abnormalities, for example, cells capable of forming tumor metastases. Acquired functional abnormalities of malignant neoplastic cells (also referred to as "characteristics of cancer") include endless replication potential, self-fulfillment in growth signals, insensitivity to anti-growth signals, avoidance from apoptosis, persistent angiogenesis And tissue invasion and metastasis.

Inducers and similar terms of apoptosis are used herein to identify compounds that induce programmed cell death in cells in contact with the compound. Apoptosis is defined as the activation of multiple biochemical events in contacted cells, such as the activation of cysteine specific proteinases (“caspases”) and fragmentation of chromatin. Induction of apoptosis in cells in contact with the compound will not necessarily be combined with inhibition of cell proliferation. Preferably, inhibition of cell proliferation and / or induction of apoptosis is specific for cells with abnormal cell growth (hyperproliferation). Thus, compared to cells with abnormal cell growth, normal proliferative or quiescent cells are less sensitive or even insensitive to compound's growth inhibition or apoptosis inducing activity. Finally, cytotoxicity is used in a more general sense to identify compounds that kill cells by various mechanisms, including induction of apoptosis / programmed cell death in a cell-cycle dependent or cell-cycle independent manner.

Cell cycle specific and similar terms are used herein to identify compounds that induce apoptosis / killing only in proliferating cells that actively pass through specific stages of the cell cycle, not in resting non-dividing cells. Continuously proliferating cells are typical in diseases such as cancer, and cells passing through all stages of the cell division cycle, namely G ("gap") 1, S ("DNA synthesis"), G2 and M ("mitotic") It is characterized by the cells in the) stage.

Compounds according to aspect A of the present invention which may be mentioned

R 1 is 1-4C-alkyl, cyclopropyl, cyclopropylmethyl, 2-4C-alkenyl, 2-4C-alkynyl, or 2-4C-alkyl substituted with R11,

R11 is -N (R111) R112, or halogen,

R111 is hydrogen, 1-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, hydroxy-2-4C-alkyl, 1-2C-alkoxy-2 -4C-alkyl, isoxazolyl, 1N- (1-3C-alkyl) -pyrazolyl, or mono-, di- or tri-fluorine-substituted 1-4C-alkyl,

R112 is hydrogen, 1-4C-alkyl, cyclopropyl, or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thio-morpholine-4 -Yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin- 1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazole-1 -Yl, triazol-1-yl, or tetrazol-1-yl,

R113 is hydrogen, 1-3C-alkyl, cyclopropyl, cyclopropylmethyl, 1-3C-alkylcarbonyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoro Ethyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl or ethyl,

Especially,

R 4 is methyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

Especially,

R5 is chlorine, bromine, fluorine, methoxy, ethoxy, difluoromethoxy or trifluoromethoxy,

R6 is hydrogen or fluorine

Wherein R 5 binds to the 5-, 7- or especially 6-position of the skeleton,

R6 binds to the 5- or 7-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Further mentionable compounds according to aspect A of the present invention

R 1 is methyl, vinyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112, fluorine, chlorine or bromine,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, vinyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, isox Sazolyl, 1N- (methyl) -pyrazolyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, vinyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2 -Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, isobutyl, tertbutyl, vinyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-meth Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl, isopropyl, or cyclopropyl, or

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N -(R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridine -1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazol-1-yl, or tetrazol-1-yl,

R113 is hydrogen, methyl, ethyl, propyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen or fluorine

Where R5 binds to the 6-position of the skeleton,

R6 binds to the 5- or 7-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Particularly worth mentioning are the compounds according to aspect A of the invention

R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-meth Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-meth Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl , 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin- 1-yl, 4N- (R113) -homopiperazin-1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, 4-methyl -Piperidin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoropiperidin-1-yl, (S) -3-fluoro-pyrrolidine- 1-yl, (R) -3-fluoro-pyrrolidin-1-yl, or 3,3-difluoro-pyrrolidin-1-yl,

R113 is methyl or acetyl, or

or

Het is pyrazol-1-yl, or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen or fluorine

Where R5 binds to the 6-position of the skeleton,

R6 binds to the 5- or in particular 7-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

More particularly mentionable compounds according to aspect A of the present invention

R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R 111 is methyl, ethyl, isopropyl, isobutyl, tertbutyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is hydrogen,

or

R 111 is methyl, ethyl, isopropyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is methyl or

or

R 111 is ethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, pyrrolidin-1-yl, azetidin-1-yl, 2,5-dihydro-pyrrole-1-yl, or 1,2,3,6-tetrahydropyridine -1- days,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen or fluorine

Where R5 binds to the 6-position of the skeleton,

R6 binds to the 7-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Compounds according to aspect A of the invention that can be highlighted

R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R 111 is methyl, ethyl, isopropyl, isobutyl, tertbutyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is hydrogen,

or

R 111 is methyl, ethyl, isopropyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is methyl or

or

R 111 is ethyl, 2-hydroxyethyl, or 2-methoxyethyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, pyrrolidin-1-yl, azetidin-1-yl, 2,5-dihydro-pyrrole-1-yl, or 1,2,3,6-tetrahydropyridine -1- days,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts, stereoisomers and salts of stereoisomers of these compounds.

Compounds according to aspect B of the invention which may be mentioned

R 1 is 1-4C-alkyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112, or halogen,

R111 is hydrogen, 1-4C-alkyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2, 2,2-trifluoroethyl,

R112 is hydrogen, 1-4C-alkyl, cyclopropyl, or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thio-morpholine-4 -Yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin- 1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazol-1-yl, or tetrazol-1-yl,

R113 is hydrogen, 1-3C-alkyl, cyclopropyl, cyclopropylmethyl, 1-3C-alkylcarbonyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoro Ethyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and 1-3C-alkyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is 1-4C-alkyl, cyclopropyl or cyclopropylmethyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Further mentionable compounds according to aspect B of the present invention

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, ethyl substituted with R 11, propyl substituted with R 11, or butyl substituted with R 11,

R11 is -N (R111) R112, fluorine, chlorine or bromine,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl, isopropyl, or cyclopropyl, or

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N -(R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazole-1 -Yl, or tetrazol-1-yl,

R113 is hydrogen, methyl, ethyl, propyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

Especially,

R 4 is methyl, ethyl, isopropyl or cyclopropyl,

More particularly,

R 4 is methyl or ethyl,

Even more particularly,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, propoxy, isopropoxy, cyclopropylmethoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

Especially,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Particularly worth mentioning are the compounds according to aspect B of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, cyclopropyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl ego,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, or 4N- (R113) -piperazin-1-yl,

R113 is hydrogen, methyl, ethyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

Wherein the Het may be substituted with one or two substituents independently selected from fluorine and methyl, or

or

Het is pyrazol-1-yl, imidazol-1-yl, or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, isopropyl or cyclopropyl,

Especially,

R 4 is methyl or ethyl,

More particularly,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, propoxy, isopropoxy, cyclopropylmethoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

Especially,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly mentionable compounds according to aspect B of the invention

R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R 111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, or cyclopropylmethyl,

R112 is hydrogen,

or

R 111 is methyl, ethyl, isopropyl, or cyclopropyl,

R112 is methyl or

or

R111 is ethyl, isopropyl, or cyclopropyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, 4N- (R113) -piperazin-1-yl, 4-methyl-pi Ferridin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoropiperidin-1-yl, (S) -3-fluoro-pyrrolidine-1- 1, (R) -3-fluoro-pyrrolidin-1-yl, 3,3-difluoro-pyrrolidin-1-yl, 3-fluoro-azetidin-1-yl, or 3, 3-difluoro-azetidin-1-yl,

R113 is hydrogen, methyl, or acetyl, or

or

Het is pyrazol-1-yl, or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, isopropyl or cyclopropyl,

Especially,

R 4 is methyl or ethyl,

More particularly,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

Especially

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

Even more particularly,

R5 is chlorine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

In one embodiment of aspect B of the invention (embodiment B1), the compounds according to aspect B of the invention that can be highlighted

R1 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclopropylmethyl, ethyl substituted with R11, propyl substituted with R11, or butyl substituted with R11,

R11 is -N (R111) R112, or halogen,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl, isopropyl, or cyclopropyl, or

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N -(R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazole-1 -Yl, or tetrazol-1-yl,

R113 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, 1-2C-alkylcarbonyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2- Trifluoroethyl,

Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmethoxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy,

Especially,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, propoxy, isopropoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

Even more particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I and salts of these compounds.

Compounds according to embodiment B1 of aspect B of the invention which may be mentioned

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112, fluorine, chlorine or bromine,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl,

R112 is methyl or

or

R111 is ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N -(R113) -piperazin-1-yl, or 4N- (R113) -homopiperazin-1-yl,

R113 is hydrogen, methyl, ethyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

Wherein the Het may be substituted with one or two substituents independently selected from fluorine and methyl, or

or

Het is pyrazol-1-yl, imidazol-1-yl, or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, propoxy, isopropoxy, cyclopropylmethoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

Especially,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

More particularly,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Further noteworthy are the compounds according to embodiment B1 of aspect B of the present invention,

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl ego,

R112 is hydrogen,

or

R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl ego,

R112 is methyl or

or

R 111 is ethyl, propyl, isopropyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl,

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, 4N- (R113) -piperazin-1-yl, 4-methyl-pi Ferridin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoro-piperidin-1-yl, (S) -3-fluoro-pyrrolidine-1 -Yl, (R) -3-fluoro-pyrrolidin-1-yl, 3,3-difluoro-pyrrolidin-1-yl, 3-fluoro-azetidin-1-yl, or 3 , 3-difluoro-azetidin-1-yl,

R113 is hydrogen, methyl, ethyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, or

or

Het is pyrazol-1-yl, or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R 5 binds to the 6-position of the skeleton;

In more specific individual embodiments,

R5 is chlorine,

In another more specific individual embodiment,

R 5 is methoxy,

In another more specific individual embodiment,

R5 is ethoxy,

In another more specific individual embodiment,

R5 is difluoromethoxy

Compounds of formula I * and salts of these compounds.

Of particular mention are the compounds according to embodiment B1 of aspect B of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl

R112 is hydrogen,

or

R111 is ethyl

R112 is hydrogen,

or

R111 is isopropyl,

R112 is hydrogen,

or

R111 is isobutyl,

R112 is hydrogen,

or

R111 is cyclopropyl,

R112 is hydrogen,

or

R111 is cyclobutyl,

R112 is hydrogen,

or

R111 is cyclopropylmethyl,

R112 is hydrogen,

or

R111 is methyl

R112 is methyl or

or

R111 is ethyl

R112 is methyl or

or

R111 is isopropyl,

R112 is methyl or

or

R111 is ethyl

R112 is ethyl

or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, 4-methyl-piperazin-1-yl, 4-acetyl-piperazin- 1-yl, 4-methyl-piperidin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoro-piperidin-1-yl, (S) -3 -Fluoro-pyrrolidin-1-yl, (R) -3-fluoro-pyrrolidin-1-yl, 3,3-difluoro-pyrrolidin-1-yl, 3-fluoro- Azetidin-1-yl, 3,3-difluoro-azetidin-1-yl, or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

Especially,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Wherein R 5 binds to the 6-position of the skeleton;

In more specific individual embodiments,

R5 is chlorine,

In another more specific individual embodiment,

R 5 is methoxy,

In another more specific individual embodiment,

R5 is ethoxy,

In another more specific individual embodiment,

R5 is difluoromethoxy

Compounds of formula I * and salts of these compounds.

More particularly to mention the compounds according to embodiment B1 of aspect B of the invention

R 1 is 2- (R 11) -ethyl,

R11 is -N (R111) R112,

R111 is hydrogen,

R112 is hydrogen,

or

R111 is methyl

R112 is hydrogen,

or

R111 is ethyl

R112 is hydrogen,

or

R111 is isopropyl,

R112 is hydrogen,

or

R111 is isobutyl,

R112 is hydrogen,

or

R111 is cyclopropyl,

R112 is hydrogen,

or

R111 is cyclobutyl,

R112 is hydrogen,

or

R111 is cyclopropylmethyl,

R112 is hydrogen,

or

R111 is methyl

R112 is methyl or

or

R111 is ethyl

R112 is methyl or

or

R111 is isopropyl,

R112 is methyl or

or

R2 and R3 together form the ring HetB including the nitrogen atoms to which they are attached,

HetB is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, 4-methyl-piperazin-1-yl, 4-acetyl-piperazin- 1-yl, or 3,3-difluoro-pyrrolidin-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy,

Especially,

R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy,

R6 is hydrogen,

Wherein R 5 binds to the 6-position of the skeleton;

In more specific individual embodiments,

R5 is chlorine,

In another more specific individual embodiment,

R 5 is methoxy,

In another more specific individual embodiment,

R5 is ethoxy,

In another more specific individual embodiment,

R5 is difluoromethoxy

Compounds of formula I * and salts of these compounds.

Compounds according to aspect C of the present invention that may be mentioned

R 1 is 1-4C-alkyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, 1-4C-alkyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, 1-4C-alkyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thio-morpholine-4 -Yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl ego,

R113 is 1-4C-alkyl, cyclopropyl or cyclopropylmethyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is 1-4C-alkyl, cyclopropyl or cyclopropylmethyl,

R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-5C-cycloalkoxy, 3-5C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy,

R6 is hydrogen

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Further mentionable compounds according to aspect C of the present invention

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, phenyl-1-2C-alkoxy, 1-4C-alkoxy-2-3C-alkoxy, 3-5C-cycloalkoxy, 3- 5C-cycloalkyl-1-2C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I and salts, stereoisomers and salts of stereoisomers of these compounds.

Particularly worth mentioning are the compounds according to aspect C of the invention

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly mentionable compounds according to aspect C of the invention

R1 is methyl, ethyl, ethyl substituted with R11, propyl substituted with R11, or butyl substituted with R11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl or ethyl,

R112 is hydrogen, methyl or ethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Even more particularly mentionable are the compounds according to aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl, ethyl, isopropyl or cyclopropyl,

R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

In one embodiment (Embodiment C1) of aspect C of the invention, the compounds according to aspect C of the invention which can be highlighted

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Compounds according to embodiment C1 of aspect C of the invention which may be mentioned

R 1 is 2-4C-alkyl substituted with methyl, ethyl, or R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrrole-1-yl, Pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Further noteworthy are the compounds according to embodiment C1 of aspect C of the present invention,

R 1 is methyl, ethyl substituted with R 11, propyl substituted with R 11 or butyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, cyclopropyloxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Of particular mention are the compounds according to embodiment C1 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly to mention the compounds according to embodiment C1 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R 4 is methyl,

R5 is chlorine, bromine, methoxy, ethoxy, or 2-methoxy-ethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

In another embodiment of aspect C of the invention (embodiment C2), the compounds according to aspect B of the invention that can be highlighted

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl,

R2 is hydrogen,

R3 is hydrogen,

R4 is ethyl

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Compounds according to embodiment C2 of aspect C of the invention which may be mentioned

R 1 is 2-4C-alkyl substituted with methyl, ethyl, or R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrrole-1-yl, Pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is ethyl

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Further noteworthy are the compounds according to embodiment C2 of aspect C of the present invention,

R 1 is methyl, ethyl substituted with R 11, propyl substituted with R 11 or butyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is ethyl

R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, cyclopropyloxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Of particular mention are the compounds according to embodiment C2 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is ethyl

R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly to mention the compounds according to embodiment C2 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached,

Het is morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is ethyl

R5 is chlorine, bromine, methoxy, ethoxy, or 2-methoxy-ethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

In another embodiment of aspect C of the invention (embodiment C3), the compounds according to aspect B of the invention that can be highlighted

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl,

R2 is hydrogen,

R3 is hydrogen,

R4 is isopropyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Compounds according to embodiment C3 of aspect C of the invention which may be mentioned

R 1 is 2-4C-alkyl substituted with methyl, ethyl, or R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrrole-1-yl, Pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is isopropyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Further noteworthy are the compounds according to embodiment C3 of aspect C of the present invention,

R 1 is methyl, ethyl substituted with R 11, propyl substituted with R 11 or butyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is isopropyl,

R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, cyclopropyloxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Of particular mention are the compounds according to embodiment C3 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is isopropyl,

R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly mentionable compounds according to embodiment C3 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is isopropyl,

R5 is chlorine, bromine, methoxy, ethoxy, or 2-methoxy-ethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

In another embodiment of aspect C of the invention (embodiment C4), the compounds according to aspect B of the invention that can be highlighted

R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, or 2-4C-alkyl substituted with R 11,

R11 is -N (R111) R112,

R 111 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl,

R112 is hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1- 1, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R113 is methyl,

R2 is hydrogen,

R3 is hydrogen,

R4 is cyclopropyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

The compounds according to embodiment C4 of aspect C of the invention which may be mentioned

R 1 is 2-4C-alkyl substituted with methyl, ethyl, or R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrrole-1-yl, Pyrazol-1-yl, imidazol-1-yl or triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is cyclopropyl,

R5 is methyl, ethyl, propyl, isopropyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmeth Oxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Further noteworthy are the compounds according to embodiment C4 of aspect C of the present invention,

R 1 is methyl, ethyl substituted with R 11, propyl substituted with R 11 or butyl substituted with R 11,

R11 is -N (R111) R112,

R111 is hydrogen or methyl,

R112 is hydrogen or methyl,

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is cyclopropyl,

R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, cyclopropyloxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy,

R6 is hydrogen,

Wherein R5 binds to the 5-, 7- or especially 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Of particular mention are the compounds according to embodiment C4 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is cyclopropyl,

R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

More particularly to mention the compounds according to embodiment C4 of aspect C of the invention

R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl,

R11 is -N (R111) R112,

R111 is methyl

R112 is methyl or

R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het,

Het is morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl or imidazol-1-yl,

R2 is hydrogen,

R3 is hydrogen,

R4 is cyclopropyl,

R5 is chlorine, bromine, methoxy, ethoxy, or 2-methoxy-ethoxy,

R6 is hydrogen,

Where R5 binds to the 6-position of the skeleton

Compounds of formula I * and salts of these compounds.

Of particular interest in compounds according to the invention means compounds of formula (I) which are included (within the scope of the invention) by one or possibly several combinations of the following specific embodiments:

Certain embodiments of a compound of formula (I) according to the invention (embodiment 1)

It means a compound of formula (I) wherein R 1 is methyl.

Certain embodiments of a compound of formula (I) according to the invention (embodiment 2)

Means a compound of formula (I) wherein R 1 is ethyl.

Certain embodiments (compound 3) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2- (R 11) -ethyl.

Certain embodiments (compound 4) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- (R 11) -propyl.

Certain embodiments (compound 5) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 4- (R 11) -butyl.

Another particular embodiment (compound 6) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2-dimethylamino-ethyl.

Another particular embodiment (compound 7) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (N-ethyl-N-methyl-amino) -ethyl.

Another particular embodiment (compound 8) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (N-isopropyl-N-methyl-amino) -ethyl.

Another particular embodiment (compound 9) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- [N- (2-hydroxyethyl) -N-methyl-amino] -ethyl.

Another specific embodiment (compound 10) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- [N- (2-methoxyethyl) -N-methyl-amino] -ethyl.

Another particular embodiment (compound 11) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2- (N-allyl-N-methyl-amino) -ethyl.

Another particular embodiment (compound 12) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (N-methyl-N-propargylamino) -ethyl.

Another particular embodiment (compound 13) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- [N-ethyl-N- (2-hydroxyethyl) -amino] -ethyl.

Another particular embodiment (compound 14) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- [N-ethyl-N- (2-methoxyethyl) -amino] -ethyl.

Another particular embodiment (compound 15) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-diethylamino-ethyl.

Another particular embodiment (compound 16) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-methylamino-ethyl.

Another particular embodiment (compound 17) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-ethylamino-ethyl.

Another specific embodiment (compound 18) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-isopropylamino-ethyl.

Another particular embodiment (compound 19) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-isobutylamino-ethyl.

Another particular embodiment (compound 20) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-cyclopropylamino-ethyl.

Another particular embodiment (compound 21) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2-cyclobutylamino-ethyl.

Another particular embodiment (compound 22) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2- (cyclopropylmethyl) amino-ethyl.

Another particular embodiment (compound 23) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-morpholin-4-yl-ethyl.

Another specific embodiment (compound 24) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-pyrrolidin-1-yl-ethyl.

Another specific embodiment (compound 25) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-azetidin-1-yl-ethyl.

Another specific embodiment (compound 26) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-piperidin-1-yl-ethyl.

Another particular embodiment (compound 27) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2- (4-methyl-piperidin-1-yl) -ethyl.

Another specific embodiment (compound 28) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-homopiperidin-1-yl-ethyl.

Another particular embodiment (compound 29) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2- (2,5-dihydropyrrole-1-yl) -ethyl.

Another particular embodiment (compound 30) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (1,2,3,6-tetrahydropyridin-1-yl) -ethyl.

Another particular embodiment (compound 31) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2-imidazol-1-yl-ethyl.

Another particular embodiment (compound 32) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (4-methyl-piperazin-1-yl) -ethyl.

Another particular embodiment (compound 33) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2- (4-acetyl-piperazin-1-yl) -ethyl.

Another particular embodiment (compound 34) of the compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-amino-ethyl.

Another particular embodiment (compound 35) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2-[(2-hydroxyethyl) -amino] -ethyl.

Another specific embodiment (compound 36) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-[(2-methoxyethyl) -amino] -ethyl.

Another specific embodiment (compound 37) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-tertbutylamino-ethyl.

Another specific embodiment (compound 38) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-allylamino-ethyl.

Another specific embodiment (compound 39) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-propargylamino-ethyl.

Another particular embodiment (compound 40) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 2-[(1-methylpropargyl) -amino] -ethyl.

Another particular embodiment (compound 41) of the compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 2-[(2,2-difluoroethyl) -amino] -ethyl.

Another specific embodiment (compound 42) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-dimethylamino-propyl.

Another particular embodiment (compound 43) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-ethylamino-propyl.

Another specific embodiment (compound 44) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-imidazol-1-yl-propyl.

Another particular embodiment (compound 45) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- (N-ethyl-N-methyl-amino) -propyl.

Another particular embodiment (compound 46) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- (N-isopropyl-N-methyl-amino) -propyl.

Another particular embodiment (compound 47) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- [N- (2-hydroxyethyl) -N-methyl-amino] -propyl.

Another specific embodiment (compound 48) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- [N- (2-methoxyethyl) -N-methyl-amino] -propyl.

Another particular embodiment (compound 49) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- (N-allyl-N-methyl-amino) -propyl.

Another particular embodiment (compound 50) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- (N-methyl-N-propargylamino) -propyl.

Another specific embodiment (compound 51) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- [N-ethyl-N- (2-hydroxyethyl) -amino] -propyl.

Another particular embodiment (compound 52) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- [N-ethyl-N- (2-methoxyethyl) -amino] -propyl.

Another particular embodiment (compound 53) of the compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3-diethylamino-propyl.

Another specific embodiment (compound 54) of the compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-methylamino-propyl.

Another specific embodiment (compound 55) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-isopropylamino-propyl.

Another particular embodiment (compound 56) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-isobutylamino-propyl.

Another specific embodiment (compound 57) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-cyclopropylamino-propyl.

Another specific embodiment (compound 58) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-cyclobutylamino-propyl.

Another particular embodiment (compound 59) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- (cyclopropylmethyl) amino-propyl.

Another specific embodiment (compound 60) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-morpholin-4-yl-propyl.

Another particular embodiment (compound 61) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-pyrrolidin-1-yl-propyl.

Another particular embodiment (compound 62) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3-azetidin-1-yl-propyl.

Another particular embodiment (compound 63) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-piperidin-1-yl-propyl.

Another specific embodiment (compound 64) of a compound of formula (I) according to the invention is

A compound of formula I, wherein R 1 is 3- (4-methyl-piperidin-1-yl) -propyl.

Another specific embodiment (compound 65) of the compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-homopiperidin-1-yl-propyl.

Another particular embodiment (compound 66) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- (2,5-dihydropyrrole-1-yl) -propyl.

Another specific embodiment (compound 67) of the compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- (1,2,3,6-tetrahydropyridin-1-yl) -propyl.

Another specific embodiment (compound 68) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3- (4-methyl-piperazin-1-yl) -propyl.

Another particular embodiment (compound 69) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3- (4-acetyl-piperazin-1-yl) -propyl.

Another particular embodiment (compound 70) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3-amino-propyl.

Another particular embodiment (compound 71) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3-[(2-hydroxyethyl) -amino] -propyl.

Another particular embodiment (compound 72) of a compound of formula (I) according to the invention

A compound of formula I wherein R 1 is 3-[(2-methoxyethyl) -amino] -propyl.

Another specific embodiment (compound 73) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-tertbutylamino-propyl.

Another specific embodiment (compound 74) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-allylamino-propyl.

Another particular embodiment (compound 75) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-propargylamino-propyl.

Another particular embodiment (compound 76) of the compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-[(1-methylpropargyl) -amino] -propyl.

Another particular embodiment (compound 77) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 3-[(2,2-difluoroethyl) -amino] -propyl.

Another particular embodiment (compound 78) of a compound of formula (I) according to the invention is

A compound of formula I wherein R 1 is 4-dimethylamino-butyl.

Another particular embodiment (compound 79) of a compound of formula (I) according to the invention is

It means a compound of formula (I) wherein R 2 is hydrogen.

Another specific embodiment (compound 80) of a compound of formula (I) according to the invention is

It means a compound of formula (I) wherein R 3 is hydrogen.

Another particular embodiment (compound 81) of a compound of formula (I) according to the invention

A compound of formula I wherein R 2 and R 3 are both hydrogen.

Another specific embodiment (compound 82) of a compound of formula (I) according to the invention is

It means a compound of formula (I) wherein R 4 is methyl.

Another specific embodiment (compound 83) of a compound of formula (I) according to the invention is

It means a compound of formula (I) wherein R 4 is ethyl.

Another particular embodiment (compound 84) of a compound of formula (I) according to the invention

It means a compound of formula (I) wherein R 4 is isopropyl.

Another particular embodiment (compound 85) of a compound of formula (I) according to the invention

A compound of formula I wherein R 4 is cyclopropyl.

Another particular embodiment (compound 86) of a compound of formula (I) according to the invention

It means a compound of formula (I) in which neither R5 nor R6 binds to the 8-position of the skeleton.

Another particular embodiment (compound 87) of a compound of formula (I) according to the invention

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 88) of a compound of formula (I) according to the invention is

R5 binds to the 5-, 6- or 7-position of the backbone,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 89) of a compound of formula (I) according to the invention is

R5 binds to the 6-position of the skeleton,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 90) of a compound of formula (I) according to the invention is

It means a compound of formula (I) wherein R 6 is fluorine.

Another particular embodiment (compound 91) of a compound of formula (I) according to the invention is

R5 binds to the 6-position of the skeleton,

R 6 binds to the 5- or in particular 7-position of the backbone and is fluorine.

Another particular embodiment (compound 92) of a compound of formula (I) according to the invention

R5 is bromine

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 93) of a compound of formula (I) according to the invention is

R5 is fluorine

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 94) of a compound of formula (I) according to the invention is

R 5 is methyl,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 95) of a compound of formula (I) according to the invention is

R 5 is methoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 96) of a compound of formula (I) according to the invention

R5 is ethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 97) of a compound of formula (I) according to the invention is

R5 is chlorine,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 98) of a compound of formula (I) according to the invention is

R5 is cyclopropylmethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 99) of a compound of formula (I) according to the invention is

R 5 is 2-methoxyethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 100) of a compound of formula (I) according to the invention is

R5 is trifluoromethyl,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 101) of a compound of formula (I) according to the invention is

R5 is trifluoromethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 102) of a compound of formula (I) according to the invention

R5 is difluoromethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another specific embodiment (compound 103) of the compound of formula (I) according to the invention is

R5 is cyclopropyloxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 104) of the compound of formula (I) according to the invention is

R5 binds to the 6-position of the skeleton and is methyl, trifluoromethyl, fluorine, chlorine, bromine, methoxy, ethoxy, 2-methoxy-ethoxy, cyclopropylmethoxy, trifluoromethoxy or difluoro Lomethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 105) of a compound of formula (I) according to the invention is

R 5 is bonded at the 6-position of the skeleton and is fluorine, chlorine, bromine, methoxy, ethoxy, difluoromethoxy or trifluoromethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 106) of a compound of formula (I) according to the invention

R 5 is bonded at the 6-position of the skeleton and is chlorine, bromine, methoxy or ethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 107) of a compound of formula (I) according to the invention is

R 5 is bonded at the 6-position of the skeleton and is chlorine, bromine, methoxy, ethoxy or difluoromethoxy,

It means a compound of formula (I) wherein R 6 is hydrogen.

Another particular embodiment (compound 108) of a compound of formula (I) according to the invention

R 5 is bonded at the 6-position of the skeleton and is chlorine, bromine, methoxy, ethoxy or difluoromethoxy,

R 6 binds to the 5-position of the skeleton and means fluorine.

Another particular embodiment (compound 109) of a compound of formula (I) according to the invention is

R 5 is bonded at the 6-position of the skeleton and is chlorine, bromine, methoxy, ethoxy or difluoromethoxy,

R 6 binds to the 7-position of the skeleton and refers to a compound of formula (I) which is fluorine.

Another particular embodiment (compound 110) of a compound of formula (I) according to the invention is

R 5 is bonded at the 6-position of the skeleton and is methoxy,

R 6 binds to the 5-position of the skeleton and means fluorine.

Another particular embodiment (compound 111) of a compound of formula (I) according to the invention is

R 5 is bonded at the 6-position of the skeleton and is methoxy,

R 6 binds to the 7-position of the backbone and is fluorine.

Another particular embodiment (compound 112) of a compound of formula (I) according to the invention is

R5 binds to the 6-position of the skeleton and is chlorine,

R 6 binds to the 7-position of the backbone and is fluorine.

Another particular embodiment of the compound of formula (I) according to the invention (embodiment 113) means a compound of formula (I *) as indicated above.

Another particular embodiment of a compound of formula (I) according to the invention (embodiment 114) means a compound of formula (Ia *) as shown below in which both R 2 and R 3 are hydrogen.

Another particular embodiment of the compound of formula (I) according to the invention (embodiment 115) is a formula in which R 2 and R 3 are both hydrogen and R 1 and R 5 have the meaning of any of 1.1 to 1.891 shown in Table 1 set forth below. Means a compound of I *.

Another particular embodiment of the compound of formula (I) according to the invention (embodiment 116) is a formula in which R 2 and R 3 are both hydrogen and R 1 and R 5 have the meaning of any of 1.1 to 1.891 shown in Table 1 set forth below. It means a compound of Ia *.

Among the specific embodiments 3 to 5 mentioned above, embodiments 3 and 4 can be highlighted, and embodiment 3 can be particularly highlighted.

Of the specific embodiments 79-81 mentioned above, embodiment 81 can be highlighted.

Among the specific embodiments 82 to 85 mentioned above, embodiments 82 and 83 can be highlighted, and embodiment 82 can be particularly highlighted.

Of the specific embodiments 86-89 mentioned above, embodiment 89 can be highlighted.

Of the specific embodiments 90-91 mentioned above, embodiment 91 can be highlighted.

Of the specific embodiments 92-103 mentioned above, embodiments 92, 93, 95, 96, 97, 101 and 102 can be highlighted, and embodiments 92, 95, 96, 97 and 102 can be particularly highlighted.

Of the specific embodiments 104-107 mentioned above, embodiments 105-107 can be highlighted.

Among the specific embodiments 108-109 mentioned above, embodiment 109 can be highlighted, and among certain embodiments 110-112, embodiments 111 and 112 can be highlighted.

It is to be understood that the present invention includes any or all possible combinations and subsets of the specific embodiments defined above.

As exemplary compounds according to the invention, the compounds of the formula (la) and salts thereof may be mentioned by the substituent meanings for R 1 and R 5 in Table 1 set forth below.

<Formula Ia *>

Where

R2 and R3 are both hydrogen,

R 4 is methyl.

As further exemplary compounds according to the invention, compounds of formula (la) * and salts thereof, wherein R2 and R3 are both hydrogen and R4 is ethyl, may be referred to by the substituent meanings for R1 and R5 in Table 1 set forth below. have.

As further exemplary compounds according to the invention, compounds of formula (Ia *) and salts thereof, wherein R2 and R3 are both hydrogen and R4 is isopropyl, are referred to by the substituent meanings for R1 and R5 in Table 1 set forth below. Can be.

As further exemplary compounds according to the invention, the compounds of formula (la) * and salts thereof, wherein R2 and R3 are both hydrogen and R4 is cyclopropyl, may be referred to by the substituent meanings for R1 and R5 in Table 1 set forth below. Can be.

As other exemplary compounds according to the invention, the compounds of the formula Ib * and salts thereof may be mentioned by the substituent meanings for R 1 and R 5 in Table 1 set forth below.

<Formula Ib *>

Where

R2 and R3 are both hydrogen,

R 4 is methyl.

As other exemplary compounds according to the invention, compounds of the general formula (Ic *) and salts thereof may be mentioned by the substituent meanings for R1 and R5 in Table 1 set forth below.

<Formula Ic *>

Where

R2 and R3 are both hydrogen,

R 4 is methyl.

Among the compounds of the formulas Ia *, Ib * and Ic *, the compounds of the formulas Ia *, Ib * and Ic * in which R 4 is methyl may each be highlighted.

Among the compounds of the formulas Ia *, Ib * and Ic *, the compounds of the formulas Ia * and Ic * in which R 4 is methyl, respectively, can be particularly emphasized.

Among the compounds of the formulas Ia *, Ib * and Ic *, the compounds of the formula Ia * in which R 4 is methyl may be more particularly emphasized.

Exemplary compounds according to the present invention may include, but are not limited to, any compound selected from the following and salts thereof.

1. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione

2. (3aS, 10R) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

3. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione

4. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione

5. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclo Penta [b] fluorene-1,3-dione

6. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

7. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

8. (3aS, 10R) -6-Bromo-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

9. (3aS, 10R) -6-Chloro-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

10. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

11. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

12. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

13. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

14. (3aS, 10R) -2- (4-Dimethylamino-butyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

15. (3aS, 10R) -2- (3-Dimethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

16. (3aS, 10R) -6-chloro-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

17. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

18. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

19. (3aS, 10R) -2- (3-Dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

20. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-imidazol-1-yl-propyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

21. (3aS, 10R) -6-cyclopropylmethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-tree Aza-cyclopenta [b] fluorene-1,3-dione

22. (3aS, 10R) -2- (2-Bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

23. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

24. (3aS, 10R) -2- (2-Bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

25. (3aS, 10R) -2- (2-Amino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

26. (3aS, 10R) -2- (2-Bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

27. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

28. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

29. (3aS, 10R) -2- (2-Azetidin-1-yl-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

30. (3aS, 10R) -2- (2-Amino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

31. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

32. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

33. (3aS, 10R) -2- (2-azetidin-1-yl-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

34. (3aS, 10R) -2- [2- (3,3-Difluoro-pyrrolidin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

35. (3aS, 10R) -2- (2-Ethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

36. (3aS, 10R) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

37. (3aS, 10R) -6-Chloro-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

38. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

39. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

40. (3aS, 10R) -6-Chloro-2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

41. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

42. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

43. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

44. (3aS, 10R) -2- (2-Azetidin-1-yl-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

45. (3aS, 10R) -2- (2-Amino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

46. (3aS, 10R) -2- (2-azetidin-1-yl-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

47. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

48. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

49. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

50. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

51. (3aS, 10R) -2- (3-Ethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

52. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione and

53. (3aS, 10R) -2- (2-cyclopropylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

Other exemplary compounds in accordance with the present invention may include, but are not limited to, any compound selected below and salts thereof.

54. (3aS, 10R) -6-Bromo-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

55. (3aS, 10R) -2- (3-Chloro-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

56. (3aS, 10R) -2- (3-Chloro-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

57. (3aS, 10R) -6-Chloro-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

58. (3aS, 10R) -6-Bromo-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

59. (3aS, 10R) -2- (3-Chloro-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

60. (3aS, 10R) -2- (2-Bromo-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

61. (3aS, 10R) -2- (2-Bromo-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

62. (3aS, 10R) -2- (2-Bromo-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

63. (3aS, 10R) -2- (3-Chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

64. (3aS, 10R) -6-Chloro-2- (3-chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

65. (3aS, 10R) -2- (3-Chloro-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

66. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -6-hydroxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

67. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

68. (3aS, 10R) -2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

69. (3aS, 10R) -2- (2-Diethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

70. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

71. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

72. (3aS, 10R) -2- (2-tert-butylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

73. (3aS, 10R) -2- [2- (2,2-Difluoro-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

74. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

75. (3aS, 10R) -10- (3-Hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

76. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

77. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

78. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

79. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

80. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

81. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

82. (3aS, 10R) -2- [2- (2-Hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

83. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

84. (3aS, 10R) -2- (2-allylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

85. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

86. (3aS, 10R) -2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

87. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

88. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

89. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

90. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

91. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (1-methyl-1H-pyrazol-3-ylamino) -ethyl ] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

92. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

93. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

94. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

95. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

96. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

97. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

98. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

99. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

100. (3aS, 10R) -6-Chloro-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a- Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

101. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

102. (3aS, 10R) -6-Chloro-2- (2-cyclopropylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

103. (3aS, 10R) -6-Chloro-2- (2-cyclobutylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

104. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

105. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

106. (3aS, 10R) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

107. (3aS, 10R) -2- (3-Diethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

108. (3aS, 10R) -6-Chloro-2- [2- (cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

109. (3aS, 10R) -6-Chloro-2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

110. (3aS, 10R) -6-Chloro-2- (2-diethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

111. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

112. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

113. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

114. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

115. (3aS, 10R) -2- (2-allylamino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

116. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

117. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

118. (3aS, 10R) -2- {2-[(2-Hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

119. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

120. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

121. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

122. (3aS, 10R) -6-Chloro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

123. (3aS, 10R) -6-Chloro-2- [2- (2,2-difluoro-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

124. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

125. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (1-methyl-1H-pyrazol-3-ylamino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

126. (3aS, 10R) -6-Chloro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

127. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

128. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

129. (3aS, 10R) -6-Chloro-2- [2- (3,3-difluoro-pyrrolidin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

130. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

131. (3aS, 10R) -6-Chloro-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

132. (3aS, 10R) -6-Chloro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

133. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

134. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (2-methyl-2H-pyrazol-3-ylamino) -ethyl ] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

135. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

136. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3-((R and S) 1-methyl-prop-2-ynylamino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

137. (3aS, 10R) -6-Chloro-2- (3-diethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

138. (3aS, 10R) -6-Chloro-2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

139. (3aS, 10R) -2- (3-allylamino-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

140. (3aS, 10R) -6-Chloro-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

141. (3aS, 10R) -2- (3-azetidin-1-yl-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

142. (3aS, 10R) -2- [3- (2,2-Difluoro-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

143. (3aS, 10R) -2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

144. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

145. (3aS, 10R) -2- [3- (2-Hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

146. (3aS, 10R) -2- (3-allylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

147. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

148. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

149. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

150. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

151. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

152. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

153. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

154. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

155. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

156. (3aS, 10R) -2- (2-tert-butylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

157. (3aS, 10R) -2- (2-allylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

158. (3aS, 10R) -6-Ethoxy-2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

159. (3aS, 10R) -6-Ethoxy-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

160. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

161. (3aS, 10R) -2- (2-cyclopropylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

162. (3aS, 10R) -2- (2-diethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

163. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

164. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

165. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

166. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

167. (3aS, 10R) -2- (3-tert-butylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

168. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

169. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

170. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

171. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

172. (3aS, 10R) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

173. (3aS, 10R) -6-Chloro-2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

174. (3aS, 10R) -6-Chloro-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a- Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

175. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

176. (3aS, 10R) -2- (3-Diethylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

177. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

178. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

179. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

180. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

181. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

182. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

183. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2 -Inyl-amino) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

184. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

185. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

186. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

187. (3aS, 10R) -6-Ethoxy-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

188. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

189. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

190. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

191. (3aS, 10R) -2- (3-allylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

192. (3aS, 10R) -6-Ethoxy-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

193. (3aS, 10R) -6-Ethoxy-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

194. (3aS, 10R) -6-Ethoxy-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

195. (3aS, 10R) -6-Ethoxy-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

196. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

197. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

198. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

199. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

200. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

201. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl ) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

202. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

203. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

204. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

205. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl ] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

206. (3aS, 10R) -2- (3-allylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

207. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

208. (3aS, 10R) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

209. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

210. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

211. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

212. (3aS, 10R) -6-Bromo-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

213. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

214. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

215. (3aS, 10R) -6-Bromo-2- (3-cyclopropylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

216. (3aS, 10R) -6-Bromo-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

217. (3aS, 10R) -6-Bromo-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

218. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

219. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

220. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

221. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

222. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

223. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

224. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

225. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

226. (3aS, 10R) -2- (3-Dimethylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

227. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

228. (3aS, 10R) -6-Bromo-2- (3-diethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

229. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

230. (3aS, 10R) -6-Bromo-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

231. (3aS, 10R) -6-Bromo-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

232. (3aS, 10R) -6-Bromo-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

233. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

234. (3aS, 10R) -6-Bromo-2- [3- (cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

235. (3aS, 10R) -6-Bromo-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

236. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl- Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

237. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl -Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

238. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

239. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl -Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

240. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazine -1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

241. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydric Oxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

242. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

243. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

244. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperi Din-1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

245. (3aS, 10R) -7-Fluoro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

246. (3aS, 10R) -7-Fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

247. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

248. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

249. (3aS, 10R) -2- (2-Ethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

250. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

251. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

252. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

253. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

254. (3aS, 10R) -2- (2-allylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

255. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

256. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

257. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

258. (3aS, 10R) -2- (2-Diethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

259. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

260. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

261. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

262. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

263. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

264. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl ) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

265. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

266. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

267. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

268. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

269. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

270. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

271. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl ] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

272. (3aS, 10R) -2- (2-Cyclobutylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

273. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

274. (3aS, 10R) -2- (2-allylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

275. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

276. (3aS, 10R) -2- (2-Diethylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

277. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

278. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

279. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

280. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

281. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

282. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

283. (3aS, 10R) -2- (2-Amino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

284. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

285. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl ) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

286. (3aS, 10R) -2- (2-Cyclopropylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

287. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-prop-2-ynylamino -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

288. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

289. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

290. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

291. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2 -Inyl-amino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

292. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl- Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

293. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperi Din-1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

294. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazine -1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

295. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydric Oxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

296. (3aS, 10R) -6-Ethoxy-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

297. (3aS, 10R) -6-Ethoxy-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

298. (3aS, 10R) -6-Ethoxy-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

299. (3aS, 10R) -6-Ethoxy-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

300. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

301. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

302. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

303. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

304. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

305. (3aS, 10R) -7-Fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

306. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

307. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

308. (3aS, 10R) -2- (3-tert-Butylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

309. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

310. (3aS, 10R) -2- (3-Dimethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

311. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

312. (3aS, 10R) -7-Fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

313. (3aS, 10R) -2- (3-Diethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

314. (3aS, 10R) -6- (1,1-difluoro-methoxy) -2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

315. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

316. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

317. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

318. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

319. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

320. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

321. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

322. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

323. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

324. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

325. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

326. (3aS, 10R) -2- [3- (3,6-Dihydro-2H-pyridin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

327. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl ) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

328. (3aS, 10R) -2- [3- (4-Acetyl-piperazin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

329. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

330. (3aS, 10R) -2- (3-Ethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

331. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

332. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

333. (3aS, 10R) -2- (3-Cyclobutylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

334. (3aS, 10R) -2- (3-allylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

335. (3aS, 10R) -6-Chloro-2- (3-dimethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

336. (3aS, 10R) -6-Chloro-2- (2-diethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

337. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

338. (3aS, 10R) -6-Chloro-2- (2-ethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

339. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

340. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

341. (3aS, 10R) -6-Chloro-2- [2- (cyclopropylmethyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

342. (3aS, 10R) -6-Chloro-7-fluoro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

343. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

344. (3aS, 10R) -6-Chloro-2- (2-cyclobutylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

345. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

346. (3aS, 10R) -2- (2-allylamino-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

347. (3aS, 10R) -6-Chloro-2- [2- (ethyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

348. (3aS, 10R) -6-Chloro-7-fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

349. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

350. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

351. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino)- Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

352. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

353. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

354. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

355. (3aS, 10R) -6-Chloro-2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

356. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

357. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

358. (3aS, 10R) -6-Chloro-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy- Phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

359. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl)- Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

360. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

361. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

362. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

363. (3aS, 10R) -2- (3-allylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

364. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

365. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

366. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

367. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl ) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

368. (3aS, 10R) -2- [3- (3,6-Dihydro-2H-pyridin-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

369. (3aS, 10R) -6-Bromo-2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

370. (3aS, 10R) -6-Bromo-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

371. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

372. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

373. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

374. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

375. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

376. (3aS, 10R) -6-Bromo-2- [2- (cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

377. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

378. (3aS, 10R) -6-Bromo-2- (2-tert-butylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

379. (3aS, 10R) -6-Bromo-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

380. (3aS, 10R) -6-Bromo-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

381. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

382. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

383. (3aS, 10R) -2- (2-allylamino-ethyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

384. (3aS, 10R) -6-Bromo-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

385. (3aS, 10R) -6-Bromo-2- (2-diethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

386. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

387. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

388. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

389. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

390. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

391. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

392. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

393. (3aS, 10R) -6-Bromo-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

394. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

395. (3aS, 10R) -6-Bromo-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

396. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

397. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

398. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

399. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

400. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

401. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

402. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl ) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

403. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

404. (3aS, 10R) -2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

405. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

406. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

407. (3aS, 10R) -2- (2-Ethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

408. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

409. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

410. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

411. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

412. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

413. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

414. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

415. (3aS, 10R) -2- (2-allylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

416. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

417. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

418. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

419. (3aS, 10R) -5-Fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

420. (3aS, 10R) -2- (2-Diethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

421. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

422. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

423. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

424. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

425. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

426. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

427. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

428. (3aS, 10R) -2- (3-Ethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

429. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

430. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

431. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

432. (3aS, 10R) -5-Fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

433. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

434. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

435. (3aS, 10R) -2- (3-cyclobutylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

436. (3aS, 10R) -2- (3-tert-Butylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

437. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

438. (3aS, 10R) -2- (3-Dimethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

439. (3aS, 10R) -5-Fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

440. (3aS, 10R) -2- (3-Diethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

441. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

442. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

443. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

444. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

445. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

446. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

447. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

448. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

449. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

450. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

451. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

452. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

453. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

454. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

455. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

456. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

457. (3aS, 10R) -6-Chloro-2- (3-ethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

458. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

459. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

460. (3aS, 10R) -6-Chloro-2- [3- (cyclopropylmethyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

461. (3aS, 10R) -6-Chloro-7-fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

462. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

463. (3aS, 10R) -6-Chloro-2- (3-cyclobutylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

464. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

465. (3aS, 10R) -2- (3-allylamino-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

466. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

467. (3aS, 10R) -6-Chloro-2- [3- (ethyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

468. (3aS, 10R) -6-Chloro-7-fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

469. (3aS, 10R) -6-Chloro-2- (3-diethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

470. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

471. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

472. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

473. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino)- Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

474. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

475. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

476. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

477. (3aS, 10R) -6-Chloro-2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

478. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

479. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

480. (3aS, 10R) -6-Chloro-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy- Phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

481. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl)- Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

482. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

483. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

484. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

485. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

486. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

487. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

488. (3aS, 10R) -6-Chloro-2- [3- (cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

489. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione and

490. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

The compounds according to the invention are analogous, for example, as described exemplarily below and according to the reaction steps detailed above, or in particular in the manner described by way of example in the following examples, or according to preparation procedures or synthetic strategies known to those skilled in the art. Or similarly prepared.

As shown in the synthetic route summarized in Scheme 1 below, ester compounds of formula IV wherein R4, R5 and R6 have the meanings described above (especially ethyl esters or especially methyl esters of formula IV), wherein R2 and R3 Condensation and cyclization of the benzaldehyde of formula III with Pictet-Spengler reaction, which have meaning, give the corresponding compounds of formulas IIa and / or IIb as mostly mixtures. The Pictet-Spungler reaction is advantageously a solvent, for example in the presence of an acid (for example trifluoroacetic acid) suitable as a catalyst or promoter, as known to those skilled in the art or as described in the examples below. It may be carried out in toluene or in particular dichloromethane at elevated or room temperature.

Compounds of formula (IV) wherein R is methyl or ethyl and R 4, R 5 and R 6 have the meanings given above are known, can be prepared analogously to the known methods or are available as described below.

Compounds of formula III are known or can be obtained in a known manner, for example by hydroxymethylation and then by formylation of the appropriate aromatic compounds via oxidation of aldehydes, or by reduction of aldehydes of suitable benzoic acid derivatives. Can be.

The compounds of formula IV can be used in the pictet-spegler reactions mentioned above as racemates or enantiomerically pure compounds. The mixture thus obtained may contain the compounds of formula (IIa) and (IIb) as diastereomers or diastereomeric racemates.

The mixture can optionally be separated by itself in a manner familiar to those skilled in the art, for example, the diastereomeric compounds of the formulas (IIa) and (IIb) can be separated, for example, by column chromatography.

If appropriate, the mixture may also be used in the next step without further separation of the diastereomers. Thereafter, separation of the diastereomers can be carried out after one of the steps involved.

When a compound of formula (IV) is used in the above-mentioned Pictet-Sppenger reaction as a racemate mixture, racemates comprising the enantiomeric compounds of formulas (IIa 'and IIb') are preferentially or in excess of the reaction Can be obtained.

Starting from the appropriate pure enantiomer of the compound of formula IV, the corresponding compound of formula IIa 'or formula IIb' (depending on the configuration of the compound of starting formula IV) can be obtained preferentially. Thus, for example, (S) -α-methyltryptophan methyl ester derivative [ie, (S) -2-amino-3- (1H-indol-3-yl) -2-methyl-propionic acid methyl ester derivative] When used in the mentioned Pictet-Spungler reaction, the corresponding compounds of the formula IIa 'are preferentially obtained.

Compounds of formula (IIa ') and (IIb') may themselves be separated from diastereomeric compounds in a manner familiar to those skilled in the art, such as by column chromatography. Similarly, the compounds of formula (IIa ') can be prepared by methods known to those skilled in the art, for example by column chromatography on chiral support materials (such as or similar to or similar to those described by way of example in the Examples below), or optical activity. It can be separated from the enantiomeric compound of formula (IIb ') by diastereomeric salt formation of the racemate compound with an acid (e.g., referred to herein below).

For example, compounds of formula (IIa 'or IIb') in enantiomerically pure form or present as racemic mixtures or with corresponding diastereomers co-produced in the Pictet-Sppenger reaction, are shown in Scheme 2 Isocyanates or corresponding activated carbamic acid esters of the formula R 1 -N═C═O, for example N-hydroxysuccinimide-activated urethanes, such as H ₃ C-NH-C (O), in the same hydantoin synthesis -OR, wherein R is 1N-succinimidyl, to yield the corresponding desired hydantoin of Formula I * (from the compound of Formula IIa ') or Formula I *** (from the compound of Formula IIb') have. The hydantoin synthesis can be carried out in a manner known in the art or as described in the Examples below, for example in the presence of microwaves.

Isocyanates of the formula R 1 -N═C═O, wherein R 1 has the meaning given above, are known or may be obtained similar or analogous to known methods. Thus, for example, a compound of formula R 1 -N═C═O, wherein R 1 is 2-7C-alkyl substituted with —N (R 111) R 112, may be used as described by way of example to those skilled in the art or in the examples below. Likewise obtained by a nucleophilic substitution reaction with the corresponding amine of formula HN (R111) R112 from a compound of formula R1-N = C = O wherein R1 is 2-7C-alkyl substituted with a suitable leaving group such as bromine can do. Thus, the isocyanates of the present invention are described, for example, in B. Akhlaghinia, Synthesis, 2005, 1955-1958, starting from the corresponding alcohol, thiol or trimethylsilyl ether, triphenylphosphine / 2,3-dichloro-5,6-dicyanobenzoquinone in acetonitrile By reaction with / Bu ₄ NOCN, it can be obtained by a substitution reaction using an isocyanate salt. Thus, the isocyanates of the present invention can be obtained from the corresponding amine compounds by isocyanate synthesis known in the art.

Alternatively, in particular when R 1 is not methyl, for example, in the enantiomerically pure form or as a racemate mixture or present with the corresponding diastereomer co-produced in the Pictet-Spegler reaction, Or the compound of formula IIb 'can be converted to the corresponding urea compound of formula VIa' (from the compound of formula IIa ') or VIb' (from the compound of formula IIb ') as shown in Scheme 3. The urea synthesis can be carried out in a manner known to those skilled in the art or as described in the Examples below, for example according to the reaction steps outlined in Scheme 4. The compound of formula VI can then be cyclized to yield the corresponding desired compound of formula I * (from the compound of formula IIa ') or I *** (from the compound of formula IIb'). The cyclization can be carried out in a manner known to those skilled in the art or as described in the Examples below.

The compounds of formulas I * and I *** can be separated from the diastereomeric compounds by themselves in a manner familiar to the person skilled in the art, for example by column chromatography. When obtaining compounds of formula (I *) and (I ***) as racemic mixtures, enantiomerically pure compounds can be obtained by separation techniques known in the art, for example the techniques described above.

Compounds of formula VIa 'or VIb' are first selected from compounds of formula LCa 'or IIb' as shown in Scheme 4, wherein X and L are suitable leaving groups, for example X is chlorine and L is 4-nitro-phenol to give the corresponding compound of formula Va 'or Vb', which is then amine of formula R1-NH ₂ , where R1 has the meaning given above. It can be obtained by reaction with to give the corresponding compound of formula VIa 'or VIb'. The reaction can be carried out in a manner known to those skilled in the art or as described in the Examples below.

R2, R3, R4, R5 and R6 have the meaning given above, R1 is 2-7C-alkyl (preferably 2-4C-alkyl) substituted by X, and X is a suitable leaving group, for example chlorine or The compound of formula (I), which is bromine, may be temporarily protected (if necessary) with an appropriate protecting group (for example, the free amino function may be temporarily protected with a tert-butyloxycarbonyl (Boc) protecting group). R 111) R 112, where R 111 and R 112 represent the groups set forth above, are reacted in a nucleophilic substitution reaction to prepare the corresponding compound of formula I wherein R 1 is 2-7C-alkyl substituted with —N (R 111) R 112. Can be. The nucleophilic substitution reaction may itself be carried out in a manner familiar to one skilled in the art or as described in the examples below or similar or similar, for example in a suitable solvent (eg acetonitrile, methanol or tetrahydrofuran, etc.). The excess of the amine of the formula HN (R111) R112 in the presence of a suitable base or optionally in the presence of microwaves at atmospheric or elevated pressure (eg in a sealed container) at room temperature, at elevated temperature or of the solvent (s) used It may be carried out at boiling / refluxing temperatures or at microwave superheated boiling temperatures.

R2, R3, R4, R5 and R6 have the meaning given above, R1 is 2-7C-alkyl (preferably 2-4C-alkyl) substituted by X, and X is a suitable leaving group, for example chlorine or Bromine compounds of formula (I) can be obtained by hydantoin synthesis as described herein using the corresponding isocyanates of formula R1-NCO. More specifically, the hydantoin synthesis is carried out in a suitable solvent (such as 2-butanone, for example when using ketones such as 2-bromo-ethylisocyanate, for example) at elevated or boiling / refluxing temperatures. .

Compounds of formula IV wherein R is methyl or ethyl and R4, R5 and R6 have the meanings given above are available as shown in Scheme 5 and as described by way of example in the examples below or similar or similar.

Starting from compounds of formula (X), in which R5 and R6 have the abovementioned meanings, the corresponding compounds of formula (VIII) can be obtained by themselves in an aminomethylation reaction (Mannich reaction) which is customary to those skilled in the art.

The compound of formula VIII is reacted in a nucleophilic substitution reaction with a compound of formula IX in which R is methyl or ethyl and R 4 has the meaning given above to give the corresponding compound of formula VII. The substitution reaction can be carried out as known to those skilled in the art or as described in the examples below or similar or analogous thereto.

The reduction of the nitro group is applied to the compound of formula VII to give the corresponding amine compound of formula VI. The reduction reaction may itself be carried out in a manner familiar to the person skilled in the art, for example by catalytic hydrogenation, for example in the presence of a noble metal catalyst such as palladium on activated carbon or in particular Raney nickel. Optionally, a catalytic amount of acid, such as hydrochloric acid, can be added to the solvent. Alternatively, the reduction can be carried out using a hydrogen-generating mixture, for example an organic acid such as acetic acid or an inorganic acid such as hydrochloric acid and a metal such as zinc, zinc-copper bond or iron.

Optionally, the ester compound of formula VI can be converted to the corresponding free acid by saponification reactions known in the art. Optionally, the free acid of the compound of formula VI may also be reconverted to the corresponding ester, in particular methyl ester, by esterification reactions known in the art, for example with thionylchloride / methanol.

Compounds of formula (IX) are known and commercially available (for example ethyl 2-nitro-propionate or ethyl 2-nitro-butyrate) or can be obtained according to known methods.

Methyl 2-nitro-propionate is described, for example, in H.L. Finkbeiner, G.W. Wagner J. Org. Chem. 1963, 28, 215-217.

More specifically, compounds of formula (IX) in which R is methyl or ethyl and R 4 has the meanings set forth above can be obtained as summarized in Scheme 6.

Compounds of formula (IX) are described, for example, in Ram et al. Synthesis 1986, 133-135, prepared by reacting a compound of formula R4-CH ₂ -NO ₂ with chloroformic ester, wherein R 4 is for example cyclopropyl, having the meaning given above, for example. can do.

Alternatively, compounds of formula (IX) are described, for example, in J. Am. Chem. Soc. 77, 6654 (1955), wherein R is a suitable leaving group, for example iodine and R4 is for example isopropyl having the meaning given above, for example R4-C (H) Compounds of L-CO ₂ R can be prepared by reaction with a suitable nitrite reagent, for example sodium nitrite or silver nitrite.

Compounds of the formulas R4-CH ₂ -NO ₂ and R4-C (H) L-CO ₂ R are known or can be obtained similar or analogous to known methods (for example, formulas R4-C (H) Compounds of L-CO ₂ R can be obtained via Finkelstein reaction); For example nitromethyl-cyclopropane is described by Helv. Chim. Acta 1982, 65, 137-161, which can be obtained, and 2-iodo-3-methyl-butyric acid ethyl ester is described in Org. Lett. 1999, 1, 1419-1422, can be obtained from 2-bromo-3-methyl-butyric acid ethyl ester as or similar to that.

Compounds of formula (X) are known or may be obtained according to known methods or as described in or in analogy with or similar to the examples below.

Thus, for example 5-methoxy-1H-indole, 5-chloro-1H-indole, 5-bromo-1H-indole, 5-fluoro-1H-indole and 5-trifluoromethyl-1H-indole Is commercially available.

Compounds of formula (X) which are ether compounds are obtained from the corresponding alcohol compounds by etherification reactions known in the art. Thus, for example, a compound of formula X wherein R 5 is hydroxyl can be converted to the corresponding ether compound in the manner as described in the examples below, or similarly or similarly.

Thus, for example, a compound of formula (X) wherein R 5 is hydroxyl may be prepared by alkylation using an appropriate alkylation reagent, where R 5 is ethoxy, propoxy, isopropoxy, cyclopropylmethoxy, difluoromethoxy or trifluoro. Can be converted to the corresponding compound of formula (X) which is romethoxy.

Enantiomerically pure starting compounds according to the invention can be obtained according to the methods as described above, for example from the corresponding racemates according to methods known in the art. Therefore, enantiomerically pure tryptophan or tryptophan derivatives (for example ester derivatives) are for example optically active acids, preferably carboxylic acids (examples of optically active acids which may be mentioned in this regard are mandelic acid, tartaric acid). , O, O'-dibenzoyltartaric acid, campoic acid, quinic acid, glutamic acid, pyroglutamic acid, malic acid, camphorsulfonic acid, 3-bromocamposulfonic acid, α-methoxyphenylacetic acid, α-methoxy-α-trifluoromethylphenyl Salt formation of the racemate compound using, but not limited to, the enantiomeric form of acetic acid and 2-phenylpropionic acid, followed by cleavage of the salt (eg (by fractionation) crystallization from a suitable solvent) and from the salt By release of the compound; Kinetic cleavage of the racemate compound, eg using a suitable lipase (for example analogous to the procedure described in Houng et al. Chirality 1996, 8, 418-422), for example corresponding Racemic cleavage by enzymes in saponification by enzymes of racemic amino acid esters; Or by stereoselective amino acid synthesis using, for example, appropriate chiral adjuvants; Or by chromatographic separation of the racemate compound on a chiral separation column.

Thus, enantiomerically pure tryptophan can be obtained, for example, as described in, or similar to, or similar to, for example, enantiomerically pure, as described in Tetrahedron Letters 39 (1998), 9589-9592. α-methyl-tryptophan, α-ethyl-tryptophan or α-isopropyl-tryptophan, respectively, start from N-Boc- (3-bromomethyl) -indole and enantiomerically pure alanine, 2-amino-butyric acid or valine Can be obtained as described in the above document.

In a more detailed example, the enantiomerically pure 5-methoxy-α-methyl-tryptophan methyl ester is the equivalent on a chiral separation column such as Daicel chiralpak AD-RH or dicel chiralpak AD-H. Chromatographic separation of racemates; Or salt formation of the corresponding racemate with an optically active acid such as mandelic acid, pyroglutamic acid or in particular (S, S) -di-p-anisoyl-tartaric acid, followed by splitting the salt [eg suitable Solvents such as ethyl acetate, acetone or in particular (by fractionation) crystallization from methanol / water] and by the release of the desired compound from the salt.

Those skilled in the art will appreciate that certain compounds according to the present invention can be converted to further compounds of the present invention by synthetic strategies known in the art and by reactions familiar to those skilled in the art.

Therefore, optionally, the compounds of formula (I) can be converted to further compounds of formula (I) by methods known to those skilled in the art. More specifically, for example

a) From the compounds of the formula (I) in which R 113 is hydrogen, the corresponding N-alkylated compounds can be obtained by reductive amination or nucleophilic substitution reactions.

b) From compounds of formula (I) wherein R 111 and / or R 112 are hydrogen, the corresponding N-alkylated compounds can be obtained by reductive amination or nucleophilic substitution reactions.

c) From a compound of formula (I) wherein R 11 is chlorine or bromine, the corresponding compound wherein R 11 is —N (R 111) R 112 may be obtained by nucleophilic substitution reaction with an amine of formula HN (R 111) R 112.

The methods mentioned in a) to c) above may be performed similarly to methods known to those skilled in the art or as described by way of example in the examples below.

Optionally the compound of formula (I) can be converted to its salt, or optionally the salt of the compound of formula (I) can be converted to the free compound. Such methods are common to those skilled in the art.

When carrying out one of the final steps or purification in the presence of an inorganic or organic acid (e.g. hydrochloric acid, trifluoroacetic acid, acetic acid or formic acid, etc.), the compound of formula I or the acid as a free base is stoichiometric or non- Compounds of formula (I) containing in stoichiometric amounts can be obtained (depending on the individual chemistry of the compound and the individual properties of the acid used). The amount of acid contained can be determined according to procedures known in the art, for example by titration or NMR.

In addition, it is known to those skilled in the art that where multiple reactive centers are present in the starting or intermediate compound, it may be necessary to temporarily block one or more reactive centers with protecting groups in order to proceed specifically with the desired reaction center. A detailed description of the use of numerous proven protectors can be found in, for example, "Protecting Group in Organic Synthesis" by T. Greene and P. Wuts (John Wiley & Sons, Inc. 1999, 3rd Ed.) Or "Protecting". Group (Thieme Foundations Organic Synthesis Series N Group "by P. Kocienski (Thieme Medical Publishers, 2000)).

The material according to the invention can be produced in a manner known per se, for example by distilling off the solvent under reduced pressure and recrystallization of the residue obtained from a suitable solvent or by means of one of the usual purification methods, such as column chromatography on a suitable support material. It is isolated and purified by application to.

Salts are suitable solvents (eg ketones such as acetone, methyl ethyl ketone or methyl isobutyl ketone, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran or dioxane, chlorinated hydrocarbons such as methylene chloride or chloroform, Obtained by dissolving the free compound in a low molecular weight aliphatic alcohol such as methanol, ethanol or isopropanol, or an ester such as ethyl acetate), the solvent containing the desired acid or base, or later Is added. Salts can be obtained by filtration, reprecipitation, precipitation with nonsolvents for addition salts, or by evaporation of the solvent. The salts obtained can be converted into the free compounds, which in turn can be converted into salts by alkalizing or acidifying. In this way, pharmacologically unacceptable salts can be converted to pharmacologically acceptable salts.

Suitably, the conversions mentioned in the present invention can be performed by themselves or similar to methods familiar to those skilled in the art.

Those skilled in the art will be able to familiarize themselves with other possible synthetic routes for the compounds according to the invention based on the knowledge of those skilled in the art and these synthetic routes shown and described in the specification of the present invention. All such other possible synthetic routes are part of the present invention.

The invention also relates to the intermediates described herein (including salts, stereoisomers and salts of these stereoisomers), methods and processes useful for synthesizing the compounds according to the invention. Accordingly, the present invention also relates to a process for the preparation of the compounds according to the invention described herein comprising at least one step of converting and / or reacting the intermediates mentioned under the conditions described herein with an appropriate reaction partner.

Although the invention has been described in detail, the scope of the invention is not limited to only the features or embodiments described above. As will be apparent to those skilled in the art, modifications, inferences, changes, inductions, correspondences and modifications to the described inventions are based on the knowledge known in the art, without departing from the spirit and scope of the invention as defined by the claims that follow. And / or in particular based on the description of the invention (eg, explicit, inherent or original).

The following examples are intended to further illustrate the invention and do not limit the invention. Similarly, further compounds according to the invention, the preparation of which is not explicitly described, can be prepared in a similar or similar manner or in a manner familiar to those skilled in the art using conventional processing techniques.

All compounds of the formula (I) and salts, stereoisomers and salts of stereoisomers thereof according to the invention, referred to in the following examples as final compounds, are preferred subjects of the invention.

In the examples, mp is melting point, h is time, min is minute, conc. Is concentrate, calc. Is calculated value, fnd. Is measured value, EF is elemental form, MS is mass spectrometry, M represents molecular ions in mass spectrometry, and the other abbreviations have their own ordinary meaning to one skilled in the art.

In addition, according to conventional practice in stereochemistry, the symbols RS and SR are used to indicate the specific configuration of each of the indicated chiral centers of the racemate. More specifically, for example, the term “(3aSR, 10RS)” refers to a racemate comprising one enantiomer having a coordination (3aS, 10R) and another enantiomer having a coordination (3aR, 10S) ; More specifically, for example, the term “(3aRS, 10RS)” refers to a racemate comprising one enantiomer having a coordination (3aR, 10R) and another enantiomer having a coordination (3aS, 10S). ; Each of the enantiomers and salts thereof, both in pure form as well as in mixtures thereof, including racemic mixtures, is part of the present invention, wherein in relation to compounds of formula I wherein R4 is methyl or ethyl, the coordination (3aS, 10R With respect to the compounds of the formula (I) in which the enantiomer having a) is a preferred part of the invention and R 4 is isopropyl or cyclopropyl, the enantiomer having a configuration (3aR, 10R) is a preferred part of the invention.

Final compound

1. (3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione

125 mg (1RS, 3SR) -6-ethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetra in a mixture of 5 ml acetonitrile and 1 ml water A solution of hydro-1H-beta-carboline-3-carboxylic acid methyl ester and 226 mg of N-succinimidyl-N-methylcarbamate was heated to 150 ° C. for 30 minutes using a microwave reactor.

Water and ethyl acetate were added to the solution. The aqueous phase was extracted with ethyl acetate and the combined organic layers were dried over magnesium sulfate. The solvent was removed under reduced pressure. After purification by column chromatography (toluene / ethylacetate 4: 1), 15 mg of the title compound were obtained as a colorless foam (MS: m / z (MH ⁺ ) = 406.1).

2. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline The title compound was prepared similar to that described in Example 1 using 3-carboxylic acid methyl ester as starting material. MS: m / z (MH ⁺ ) = 436.1

3. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6-methoxy-2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl The title compound was prepared in analogy to that described in Example 1 using ester as starting material. MS: m / z (MH ⁺ ) = 392.1

4. (3aSR, 10RS) -6-Bromo-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza Cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 1 using compound A4 as starting material. MS: m / z (MH ⁺ ) = 440.0 / 442.0, mp: 248 to 251 ° C

5. (3aSR, 10RS) -6-Chloro-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclo Penta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 1 using compound A5 as starting material. MS: m / z (MH <+>) = 396.0, m.p .: 248-250 degreeC

6. (3aSR, 10RS) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

100 mg (240 μmol) of (1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3 in 4 ml of dichloromethane To a suspension of 4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester was added 126 μl (970 μmol, 4.00 equiv) of triethylamine. The solution was cooled to 0 ° C. and a solution of 123 mg (610 μmol, 2.5 equiv) of 4-nitrophenyl chloroformate in 1 ml dichloromethane was added dropwise. The mixture was stirred at 0 ° C. for 10 minutes and at room temperature for an additional 30 minutes. The solution was cooled back to 0 ° C. and 72.0 μl (660 μmol, 2.7 equiv) in 1 ml of dichloromethane were added slowly. The mixture was allowed to warm to rt overnight.

Water and saturated aqueous sodium carbonate solution were added and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate and the solvent was removed under reduced pressure (210 mg crude intermediate).

The crude intermediate was dissolved in 5 ml of acetone and the solution was heated to 150 ° C. for 60 minutes using a microwave reactor. The solvent was removed under reduced pressure. After purification by column chromatography, 24.5 mg of (3aSR, 10RS) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione was obtained (m / z (MH ⁺ ) = 493.2 ).

7. (3aSR, 10RS) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared similar to that described in Example 6 using -carboline-3-carboxylic acid methyl ester. m / z (MH ⁺ ) = 449.2

Alternatively, (+/-)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro The title compound can be obtained using -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and dimethylamine as starting materials.

7a. (+)-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, 10a-triaza-cyclopenta [b] fluorene-1,3-dione

(+)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The title compound was prepared similar to that described in Example 30, using 10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24a) and dimethylamine as starting materials.

(+)-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The absolute stereochemistry of 10a-triaza-cyclopenta [b] fluorene-1,3-dione is (3aR, 10S) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

MS: m / z (MH ⁺ ) = 449.2; [α] ²⁰ _D = + 157 ° (c = 0.5400, methanol)

7b. (-)-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, 10a-triaza-cyclopenta [b] fluorene-1,3-dione

(-)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The title compound was prepared similar to that described in Example 30, using 10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24b) and dimethylamine as starting materials.

(-)-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The absolute stereochemistry of 10a-triaza-cyclopenta [b] fluorene-1,3-dione is (3aS, 10R) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

MS: m / z (MH ⁺ ) = 449.3; [α] ²⁰ _D =-159 ° (c = 0.5400, methanol)

8. (3aSR, 10RS) -6-Bromo-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -6-bromo-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared similar to that described in Example 6 using -carboline-3-carboxylic acid methyl ester. m / z (MH ⁺ ) = 497.2 / 499.1, mp: 286 ° C to 288 ° C

9. (3aSR, 10RS) -6-Chloro-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -6-chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β- instead of -3-carboxylic acid methyl ester The title compound was prepared similar to that described in Example 6 using carboline-3-carboxylic acid methyl ester. m / z (MH ⁺ ) = 453.2, mp: 283 ° C to 286 ° C.

10. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared analogously to that described in Example 6 using -carboline-3-carboxylic acid methyl ester and N- (2-aminoethyl) -morpholine instead of 2-dimethylaminoethyl amine. m / z (MH ⁺ ) = 491.2, mp: 260 ° C to 263 ° C.

11. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared analogously to that described in Example 6 using -carboline-3-carboxylic acid methyl ester and 1- (2-aminoethyl) -pyrrolidine in place of 2-dimethylaminoethyl amine . m / z (MH ⁺ ) = 475.2, mp: 252 ° C to 255 ° C.

12. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester Carboline-3-carboxylic acid methyl ester and 1- (2-aminoethyl) -4-methyl piperazine in place of 2-dimethylaminoethyl amine to give the title compound similar to that described in Example 6. Prepared. m / z (MH ⁺ ) = 504.2, mp: 224 ° C to 227 ° C.

13. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared analogously to that described in Example 6 using -carboline-3-carboxylic acid methyl ester and 2- (imidazol-1-yl) -ethyl amine instead of 2-dimethylaminoethyl amine It was. m / z (MH ⁺ ) = 472.2, mp: 321 ° C to 324 ° C.

14. (3aSR, 10RS) -2- (4-Dimethylamino-butyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared analogously to that described in Example 6 using -carboline-3-carboxylic acid methyl ester and 4- (dimethylamino) -butyl amine instead of 2-dimethylaminoethyl amine. m / z (M−H ⁺ ) = 477.3.

15. (3aSR, 10RS) -2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β instead of 3-carboxylic acid methyl ester The title compound was prepared analogously to that described in Example 6 using -carboline-3-carboxylic acid methyl ester and 3-dimethylaminopropyl amine instead of 2-dimethylaminoethyl amine. m / z (MH ⁺ = 463.2), mp: 228 ° C to 231 ° C.

(1RS, 3SR) -6-ethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl The following compounds can be prepared using procedures similar to those achieved in Example 6 starting from the ester but selecting the appropriate amine as the reaction partner:

(3aSR, 10RS) -2- (2-dimethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (3-dimethylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline The following compounds can be prepared using procedures similar to those achieved in Example 6 starting from the 3-carboxylic acid methyl ester but selecting the appropriate amine as the reaction partner:

(3aSR, 10RS) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2- (2-morpholin-4-yl-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2- [2- (4-methyl-piperazin-1-yl) -ethyl]- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

Starting from compound A4 mentioned below, however, the following compounds can be prepared using procedures similar to those achieved in Example 6 by selecting the appropriate amine as the reaction partner:

(3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -2- (2-morpholin-4-yl-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9 , 10a-triaza-cyclopenta [b] fluorene-1,3-dione.

Starting from compound A5 mentioned below, however, the following compounds can be prepared using procedures similar to those achieved in Example 6 by selecting the appropriate amines as reaction partners:

(3aSR, 10RS) -6-Bromo-10- (3-hydroxy-phenyl) -2- (2-morpholin-4-yl-ethyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-10- (3-hydroxy-phenyl) -2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

Starting from the appropriate compounds A6 to A10 mentioned below, the following compounds can be prepared using procedures similar to those achieved in Example 1:

(3aSR, 10RS) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -2-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-2-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-Bromo-3a-ethyl-10- (3-hydroxy-phenyl) -2-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-Chloro-3a-ethyl-10- (3-hydroxy-phenyl) -2-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclo Penta [b] fluorene-1,3-dione.

The following compounds can be prepared using procedures similar to those achieved in Example 6 starting from the appropriate compounds A6 to A10 mentioned below and selecting the appropriate amines as reaction partners:

(3aSR, 10RS) -2- (2-dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (2-dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-2- (2-dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-2- (2-dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2,9 , 10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6-methoxy-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (4-dimethylamino-butyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (3-dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (2-dimethylamino-ethyl) -3a-ethyl-6-ethoxy-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (3-dimethylamino-propyl) -6-ethoxy-3a-ethyl-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2- [2- (4-methyl-piperazin-1-yl ) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6- (2-methoxy-ethoxy) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (3-dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-Chloro-3a-ethyl-10- (3-hydroxy-phenyl) -2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-chloro-2- (3-dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2,9 , 10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-Bromo-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-3a-ethyl-10- (3-hydroxy-phenyl) -2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-3a-ethyl-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -6-bromo-2- (3-dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

16. (3aSR, 10RS) -6-chloro-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -6-Chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester And 3-dimethylaminopropyl amine as starting material to prepare the title compound similar to that described in Example 6. MS: m / z (MH ⁺ ) = 467.2

17. (3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10 -Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -6-Chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester And 1- (2-aminoethyl) -pyrrolidine as starting material to prepare the title compound similar to that described in Example 6. MS: m / z (MH ⁺ ) = 479.2

18. (3aSR, 10RS) -2- (2-Dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -3-Ethyl-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl The title compound was prepared similar to that described in Example 6 using ester as starting material. MS: m / z (MH ⁺ ) = 463.2

19. (3aSR, 10RS) -2- (3-Dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -3-Ethyl-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl The title compound was prepared similar to that described in Example 6 using ester and 3-dimethylaminopropyl amine as starting materials. MS: m / z (MH ⁺ ) = 477.2

20. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -2- (3-imidazol-1-yl-propyl) -6-methoxy-3a-methyl-3a, 4,9,10 -Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 6 using N- (3-aminopropyl) -imidazole as starting material. MS: m / z (MH ⁺ ) = 486.2

21. (3aSR, 10RS) -6-cyclopropylmethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-tree Aza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -6-cyclopropylmethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxyl The title compound was prepared similar to that described in Example 1 using acid methyl ester as starting material. MS: m / z (MH ⁺ ) = 432.0

22. (3aSR, 10RS) -2- (2-Bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

500 mg (1.31 mmol) of (1RS, 3SR) -6-ethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetra in 25 ml 2-butanone To the solution of hydro-1H-beta-carboline-3-carboxylic acid methyl ester was added 120 μl (1.31 mmol) bromoethyl isocyanate. The mixture was heated to reflux for 24 hours. The solvent was removed under reduced pressure. The crude product was purified by column chromatography (silica gel; toluene, ethyl acetate 6: 1). 260 mg (40%) of the title compound were obtained as a colorless solid. mp: 250-252 ° C., MS: m / z (MH ⁺ ) = 498.1 / 500.0

23. (3aSR, 10RS) -2- (2-Dimethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

200 mg (3aSR, 10RS) -2- (2-bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 in 10 ml of acetonitrile 200 μl of a 2 M solution of dimethyl amine in tetrahydrofuran in a suspension of 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 22) and 85 mg of sodium carbonate was added. The mixture was heated to reflux and an additional 1 ml of dimethyl amine 2 M solution in THF was added. After heating to reflux for an additional 2 hours, an additional 600 μl of a solution of dimethyl amine in THF was added. The mixture was heated to reflux for 15 hours. Water was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. After the solvent was removed under reduced pressure, the residue was triturated with diisopropyl ether. 82 mg (44%) of the title compound were obtained as a colorless solid. MS: m / z (MH ⁺ ) = 463.2

24. (3aSR, 10RS) -2- (2-Bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

3.17 g (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H- in 35 ml 2-butanone To the solution of beta-carboline-3-carboxylic acid methyl ester was added 860 μl bromoethyl isocyanate. The mixture was heated to reflux for 7 hours and stirred at room temperature overnight. The precipitated compound was filtered off and washed with 2-butanone. 3.09 g (74%) of the title compound were obtained. mp: 299-302 ° C., MS: m / z (MH ⁺ ) = 484.0 / 486.0

24a. (+)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, 10a-triaza-cyclopenta [b] fluorene-1,3-dione

(-)-1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester The title compound was prepared similar to that described in Example 24 using the starting material.

(+)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The absolute stereochemistry of 10a-triaza-cyclopenta [b] fluorene-1,3-dione is (3aR, 10S) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

MS: m / z (MH ⁺ ) = 482.1 / 484.1; [α] ²⁰ _D = + 115 ° (c = 0.8550, methanol)

24b. (-)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, 10a-triaza-cyclopenta [b] fluorene-1,3-dione

(+)-1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester The title compound was prepared similar to that described in Example 24 using the starting material.

(-)-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9, The absolute stereochemistry of 10a-triaza-cyclopenta [b] fluorene-1,3-dione is (3aS, 10R) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

MS: m / z (MH ⁺ ) = 482.3 / 484.3; [α] ²⁰ _D =-108 ° C (c = 0.5450, methanol)

25. (3aSR, 10RS) -2- (2-Amino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

150 mg (3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 in 2 ml methanol To a solution of, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) was added 1 ml of a 7 M solution of ammonia in methanol. The mixture was heated in a sealed tube to 130 ° C. for 20 minutes and 140 ° C. for an additional 60 minutes using a microwave reactor. Water was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. After evaporation of the solvent under reduced pressure, the crude product was purified by column chromatography (silica gel; ethyl acetate, methanol, ammonia 10: 0.3: 0.2). After trituration with diisopropyl ether, crystallization gave 90 mg of oil. 62 mg (48%) of the title compound were obtained as a colorless solid. MS: m / z (MH ⁺ ) = 421.1

26. (3aSR, 10RS) -2- (2-Bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

1.66 g (5.39 mmol) of (1RS, 3SR) -6-chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro in 20 ml 2-butanone 490 μl of 2-bromoethyl isocyanate was added to a suspension of -1H-beta-carboline-3-carboxylic acid methyl ester. After the mixture was heated to reflux for 4 hours, an additional 490 μl of 2-bromoethyl isocyanate was added and the mixture was heated to reflux overnight. The solvent was removed at reduced pressure and the residue was dissolved in 20 ml of dimethyl formamide. The mixture was stirred at 80 ° C for 15 h. The solvent was removed at reduced pressure and the residue was dissolved in ethyl acetate. Water was added and the organic layer was dried over magnesium sulfate. The solvent was removed at reduced pressure and the residue was suspended in a mixture of toluene and ethyl acetate (4: 1). The suspension was filtered. 1.35 g (62%) of the title compound were obtained as a precipitate. mp: 262 to 264 ° C., MS: m / z (MH ⁺ ) = 488.0 / 490.0

27. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

150 mg (3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4 in 5 ml of acetonitrile 66 mg sodium carbonate in a solution of 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24), and methyl in tetrahydrofuran 920 μl 2 M solution of amine was added. The mixture was heated in a sealed tube at 140 ° C. for 3 hours using a microwave reactor. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure. Purification by column chromatography (silica gel; ethyl acetate, methanol, ammonia 10: 1: 0.5) and trituration with diisopropylether gave 60 mg of the title compound as a colorless solid. MS: m / z (MH ⁺ ) = 435.1

28. (3aSR, 10RS) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-Bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9 The title compound was prepared similar to that described in Example 27 (426160) using, 10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 26) as starting material. MS: m / z (MH ⁺ ) = 439.1

29. (3aSR, 10RS) -2- (2-azetidin-1-yl-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

200 mg (3aSR, 10RS) -2- (2-bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 in 5 ml acetonitrile In a solution of 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 26), 87 mg of sodium carbonate and 83 μl of azetidine Added. The mixture was heated to reflux for 4 hours. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure. Purification by column chromatography (silica gel; ethyl acetate, methanol, ammonia 10: 0.2: 0.1) and trituration with diisopropylether gave 61 mg of the title compound as a colorless solid. MS: m / z (MH ⁺ ) = 465.1

30. (3aSR, 10RS) -2- (2-amino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

200 mg (3aSR, 10RS) -2- (2-bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 in 3 ml methanol To a solution of 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 26) was added 1.2 ml of a 7 M solution of ammonia in methanol. The mixture was heated in a sealed tube at 140 ° C. for 1 hour using a microwave reactor. The solvent was removed under reduced pressure. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The solvent was removed under reduced pressure. The crude product was purified by preparative HPLC. 24 mg of the title compound were obtained. MS: m / z (MH ⁺ ) = 425.1

31. (3aSR, 10RS) -6-chloro-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 29, using imidazole as a starting material instead of azetidine. MS: m / z (MH ⁺ ) = 476.2

32. (3aSR, 10RS) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 29 using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and N-acetyl piperazine as starting materials . MS: m / z (MH ⁺ ) = 532.1

33. (3aSR, 10RS) -2- (2-azetidin-1-yl-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 29, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) as starting material. MS: m / z (MH ⁺ ) = 461.1

34. (3aSR, 10RS) -2- [2- (3,3-Difluoro-pyrrolidin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 27 using 3,3-difluoropyrrolidine hydrochloride as starting material. MS: m / z (MH ⁺ ) = 511.1

35. (3aSR, 10RS) -2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, Similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24), and a 2 M solution of ethyl amine in methanol as starting material The compound was prepared. MS: m / z (MH ⁺ ) = 449.1

36. (3aSR, 10RS) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

5.5 mg (1RS, 3SR) -6- (1,1-difluoro-methoxy) -1- (3-hydroxy-phenyl) -3-methyl-2,3 in 10 ml 2-butanone To the solution of, 4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester was added 132 μl of bromoethyl isocyanate. The mixture was heated to reflux for 30 minutes. Aqueous sodium bicarbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solvent was removed at reduced pressure. After purification by column chromatography (silica gel; toluene, ethyl acetate 4: 1) and triturated with diisopropylether, 550 mg (61%) of the title compound were obtained as a colorless solid. MS: m / z (MH ⁺ ) = 519.9 / 522.0

37. (3aSR, 10RS) -6-Chloro-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 30, using a 2 M solution of ethyl amine in methanol as starting material. MS: m / z (MH ⁺ ) = 453.2

38. (3aSR, 10RS) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 30 using isopropyl amine as starting material. MS: m / z (MH ⁺ ) = 467.2

39. (3aSR, 10RS) -6-Chloro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 29, using N-isopropyl methyl amine as starting material instead of azetidine. MS: m / z (MH ⁺ ) = 481.2

40. (3aSR, 10RS) -6-Chloro-2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

The title compound was prepared similar to that described in Example 29, using N-ethyl methyl amine as starting material instead of azetidine. MS: m / z (MH ⁺ ) = 467.1

41. (3aSR, 10RS) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, Example 29 using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 22), and a 2 M solution of methyl amine in tetrahydrofuran in place of azetidine as starting material The title compound was prepared similar to that described. MS: m / z (MH ⁺ ) = 449.1

42. (3aSR, 10RS) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 2M solution of, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 36), and methyl amine in tetrahydrofuran, starting material To give the title compound similar to that described in Example 30. MS: m / z (MH ⁺ ) = 471.2

43. (3aSR, 10RS) -6- (1,1-difluoro-methoxy) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 36), and dimethyl amine as starting material instead of azetidine The title compound was prepared similar to that described in Example 29. MS: m / z (MH ⁺ ) = 485.2

44. (3aSR, 10RS) -2- (2-azetidin-1-yl-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 36) as starting material, titled similarly as described in Example 29 The compound was prepared. MS: m / z (MH ⁺ ) = 497.2

45. (3aSR, 10RS) -2- (2-Amino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 22) as starting material. MS: m / z (MH ⁺ ) = 435.1

46. (3aSR, 10RS) -2- (2-azetidin-1-yl-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 29, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione as starting material. MS: m / z (MH ⁺ ) = 475.2

47. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and isopropyl amine as starting materials. MS: m / z (MH ⁺ ) = 463.2

48. (3aSR, 10RS) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, Preparation of the title compound similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and C-cyclopropyl methyl amine as starting materials It was. MS: m / z (MH ⁺ ) = 475.2

49. (3aSR, 10RS) -10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and isobutyl amine as starting materials. MS: m / z (MH ⁺ ) = 477.2

50. (3aSR, 10RS) -2- (2-cyclobutylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and cyclobutyl amine as starting materials. MS: m / z (MH ⁺ ) = 475.2

51. (3aSR, 10RS) -2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and ethyl amine as starting materials. MS: m / z (M ⁺ H) = 463.2

52. (3aSR, 10RS) -2- [2- (Ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and N-ethyl methyl amine as starting materials. . MS: m / z (MH ⁺ ) = 463.2

53. (3aSR, 10RS) -2- (2-cyclopropylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(3aSR, 10RS) -2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2, The title compound was prepared similar to that described in Example 30, using 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 24) and cyclopropyl amine as starting materials. MS: m / z (MH ⁺ ) = 461.2

The following compounds can be prepared using procedures similar to those described in Examples 22, 24, 26 or 36, starting from the appropriate starting compounds mentioned below, and selecting bromoethyl isocyanate as the reaction partner:

(3aSR, 10RS) -6-bromo-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (2-Bromo-ethyl) -6-cyclopropylmethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione,

(3aSR, 10RS) -2- (2-Bromo-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-6-trifluoromethoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione.

54. (3aSR, 10RS) -6-Bromo-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -6-Bromo-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl Starting from the ester, the title compound was prepared similar to the procedure described in Example 22. MS: m / z (MH ⁺ ) ^- = 531.9 / 533.8

55. (3aSR, 10RS) -2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3- The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 454.0

55a. (3aS, 10R) -2- (3-Chloro-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9 , 10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1R, 3S) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3- The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 454.0

56. (3aSR, 10RS) -2- (3-Chloro-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -6- (1,1-difluoro-methoxy) -1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro The title compound was prepared similar to the procedure described in Example 22 using -1H-beta-carboline-3-carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 490.0

57. (3aSR, 10RS) -6-Chloro-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -6-chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carbox The title compound was prepared similar to the procedure described in Example 22 using acidic methyl ester. MS: m / z (MH ⁺ ) = 457.9

58. (3aSR, 10RS) -6-Bromo-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -6-bromo-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3- The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 501.9 / 503.9

59. (3aSR, 10RS) -2- (3-Chloro-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -6-ethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3- The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 468.1

60. (3aSR, 10RS) -2- (2-Bromo-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -7-Fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid Starting from the methyl ester, the title compound was prepared similar to the procedure described in Example 22. MS: m / z (MH ⁺ ) = 502.0

61. (3aSR, 10RS) -2- (2-Bromo-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -6-Chloro-7-fluoro-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl Starting from the ester, the title compound was prepared similar to the procedure described in Example 22. MS: m / z (MH ⁺ ) ^- = 505.9

62. (3aSR, 10RS) -2- (2-Bromo-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

(1RS, 3SR) -5-Fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid Starting from the methyl ester, the title compound was prepared similar to the procedure described in Example 22. MS: m / z (MH ⁺ ) = 501.9 / 503.8

63. (3aSR, 10RS) -2- (3-Chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -7-fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3 The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 472.0

64. (3aSR, 10RS) -6-Chloro-2- (3-chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -6-chloro-7-fluoro-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3- The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) ^- = 474.0

65. (3aSR, 10RS) -2- (3-Chloro-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

Chloropropyl isocyanate and (1RS, 3SR) -5-fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3 The title compound was prepared similar to the procedure described in Example 22 using carboxylic acid methyl ester. MS: m / z (MH ⁺ ) = 472.0

66. (3aSR, 10RS) -2- (2-Dimethylamino-ethyl) -6-hydroxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione

150 mg (3aSR, 10RS) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4 in 5 ml of dichloromethane A solution of 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione (Example 7) was cooled to -78 ° C. 20 ml of boron tribromide was added dropwise. The suspension was stirred at -78 ° C for 30 minutes and allowed to warm to room temperature. After stirring for 1 hour at room temperature, the mixture was cooled to 0 ° C. and aqueous sodium bicarbonate solution was added. The organic layer was separated and dried over magnesium sulfate. The solvent was removed at reduced pressure. After purification by column chromatography (silica gel, ethyl acetate, methanol, ammonia 10: 0.3: 0.2), 49 mg of the title compound were obtained as a colorless foam. MS: m / z (MH ⁺ ) = 435.2

General Procedure for the Preparation of Examples 67-544

A solution of the indicated starting material (1 equiv) and the indicated amine (20 equiv) in THF was heated to 150 ° C. using a sealed tube. In some cases, catalytic amounts of sodium iodide were added to promote the reaction. The reaction was monitored by LC-MS. After complete conversion (24-48 hours), the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and extracted with aqueous sodium bicarbonate solution. The organic layer was separated and the solvent removed. The final compound was purified by preparative HPLC and then lyophilized.

General procedure for the preparation of the salts given in the table below:

A mixture of 100 mg of the appropriate free base, 1.00 equivalent of the corresponding acid and 1 ml of the indicated solvent was heated to reflux. The solution was allowed to cool to room temperature. The precipitated salt was filtered off, washed with solvent and dried at 40 ° C. under reduced pressure. Some examples contain traces of solvent.

Starting compound

A1. (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl Esters and (1RS, 3RS) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxyl Acid methyl ester

(+/-)-2-amino-3- (5-methoxy-1H-indol-3-yl) -2-methyl-propionic acid methyl ester (5.178 g, 19.5 mmol) in anhydrous dichloromethane (80 ml) and To a solution of 3-hydroxybenzaldehyde (2.85 g, 23.4 mmol, 1.2 equiv) was added trifluoroacetic acid (1.5 ml, 19.5 mol, 1 equiv) and the mixture was stirred at room temperature under argon. When TLC showed that (+/-)-2-amino-3- (5-methoxy-1H-indol-3-yl) -2-methyl-propionic acid methyl ester was lost (day 1), some methanol Was added to dissolve the precipitated product during the reaction. The mixture was then diluted with dichloromethane (750 ml) and washed with 2 M aqueous HCl, aqueous NaHCO ₃ and water, dried and concentrated. The residue was purified by column chromatography (dichloromethane-ethyl acetate 9: 1 to 7: 1) to give 5.22 g (73%) of (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-meth Oxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (mp 183-184 ° C. from ethyl acetate-light petroleum) and 1.07 g (15%) of (1RS, 3RS) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline- 3-carboxylic acid methyl ester (mp 175-177 ° C. via ethyl acetate-) was obtained.

According to NMR experiments (eg, nuclear Overhauser effect), the main product of the Pictet-Spengler reaction is a diastereomer with coordination (1RS, 3SR). This diastereomer has a higher retention factor than the side product with coordination (1RS, 3RS) (silica gel, ethyl acetate-light ether).

(1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl Enantiomeric Separation of Esters:

58.4 g of racemate (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline- 3-carboxylic acid methyl ester was separated into its enantiomers by preparative HPLC using the following conditions:

Column: CHIRALPAK AD 20 μm, 250 × 50 mm

Mobile phase: n-heptane / ethanol / diethylamine 60/40 / 0.1 (v / v / v)

Flow rate: 120 ml / min

Detection: UV 315 nm

Temperature: 25 ℃

29.1 g of (-)-1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid Methyl ester {τ = 6.5 min,> 99.5% ee, [α] ²⁰ _D = -53 ° (c = 0.5200, methanol)} and 27.6 g of (+)-1- (3-hydroxy-phenyl) -6 -Methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester {τ = 12.7 min, greater than 99.0% ee, [a] ²⁰ _D = + 54 ° (c = 0.5150, methanol)}.

Of (+)-1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester Absolute stereochemistry is (1R, 3S) -1- (3-hydroxy-phenyl) -6-methoxy-3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3- Temporarily designated as carboxylic acid methyl ester.

A2. (1RS, 3SR) -6-ethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

(+/-)-2-amino-3- (5-ethoxy-1H-indol-3-yl) -2-methyl-propionic acid methyl ester (829 mg, 3 mmol) in anhydrous dichloromethane (40 ml), A mixture of 3-hydroxybenzaldehyde (439 mg, 3.6 mmol) and trifluoroacetic acid (223 μl, 3 mmol) was stirred under argon for 6 hours. Methanol (2 ml) was added to dissolve the precipitated product and the mixture was diluted with dichloromethane (150 ml). It was washed with saturated aqueous NaHCO ₃ (2 × 50 ml) and water (2 × 50 ml), dried and the solvent was removed under reduced pressure. The residue was purified by column chromatography (dichloromethane ethyl acetate, 7: 1-&gt; 4: 1) to (1RS, 3SR) -1- (3-hydroxy-phenyl) -6-ethoxy-3-methyl-2 , 3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (1.05 g, 93%) was obtained. mp 173-175 ° C. (from ethyl acetate-hexane).

A3. (1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline 3-carboxylic acid methyl ester and (1RS, 3RS) -1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9- Tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

(+/-)-2-amino-3- [5- (2-methoxy-ethoxy) -1H-indol-3-yl] -2-methyl-propionic acid methyl ester in anhydrous dichloromethane (20 ml) To a solution of 800 mg, 2.60 mmol) and 3-hydroxybenzaldehyde (383 mg, 3.14 mmol, 1.2 equiv) was added trifluoroacetic acid (200 μl, 2.6 mmol, 1 equiv) and the mixture was stirred at room temperature under argon. Stirred. When TLC showed disappearance of starting material (day 1), some methanol was added to dissolve the precipitated product. Then it was diluted with CH ₂ Cl ₂ (250 ml) and washed with 2M aqueous HCl, aqueous NaHCO ₃ and water, dried and concentrated. The residue was purified by column chromatography (dichloromethane-ethyl acetate, 7: 1-&gt; 5: 1) to (1RS, 3SR) -1- (3-hydroxy-phenyl) -6- (2-methoxy- Methoxy) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (839 mg, 78%) and (1RS, 3RS) -1- (3 -Hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester (152 mg, 14%).

A4. (1RS, 3SR) -6-Chloro-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. m.p .: 240-241 degreeC

A5. (1RS, 3SR) -6-Bromo-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. m / z (MH ⁺ ) = 415.0 / 417.1, mp: 240-241 ° C.

Starting from the appropriate compounds B6 to B10, the following compounds A6 to A10 can be prepared using procedures similar to those achieved for compound A1.

A6. (1RS, 3SR) -3-Ethyl-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl ester; MS: m / z (MH ⁺ ) = 394.9

A7. (1RS, 3SR) -6-Ethoxy-3-ethyl-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl ester

A8. (1RS, 3SR) -3-ethyl-1- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2,3,4,9-tetrahydro-1H-beta-carboline 3-carboxylic acid ethyl ester

A9. (1RS, 3SR) -6-Chloro-3-ethyl-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl ester

A10. (1RS, 3SR) -6-Bromo-3-ethyl-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid ethyl ester

A11. (1RS, 3SR) -6-cyclopropylmethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxyl Acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. MS: m / z (MH ⁺ ) = 406.9

A12. (1RS, 3SR) -6- (1,1-difluoro-methoxy) -1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β Carboline-3-carboxylic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. MS: m / z (MH ⁺ ) = 402.9

A13. (1RS, 3SR) -6-trifluoromethoxy-1- (3-hydroxy-phenyl) -3-methyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxyl Acid methyl ester

Starting from the appropriate starting compound, the title compound can be prepared similar to the procedure described for compound A1.

Starting from the appropriate compounds B14 to B16, the following compounds A14 to A16 can be prepared using procedures similar to those achieved for compound A1.

A14. (1RS, 3SR) -6-cyclopropylmethoxy-3-ethyl-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-β-carboline-3-carboxyl Acid ethyl ester

A15. (1RS, 3SR) -6- (1,1-difluoro-methoxy) -3-ethyl-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-β Carboline-3-carboxylic acid ethyl ester

A16. (1RS, 3SR) -3-ethyl-1- (3-hydroxy-phenyl) -6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxyl Acid ethyl ester

A17. (1RS, 3SR) -5-Fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid Methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. m / z (MH ⁺ ) = 385

A18. (1RS, 3SR) -7-Fluoro-1- (3-hydroxy-phenyl) -6-methoxy-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid Methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. m / z (MH ⁺ ) = 385.0

A19. (1RS, 3SR) -6-Chloro-7-fluoro-1- (3-hydroxy-phenyl) -2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound A1. m / z (MH ⁺ ) = 389

B1. (+/-)-2-amino-3- (5-methoxy-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Wet Raney Nickel in a solution of (+/-)-3- (5-methoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester (4.26 g) in methanol (80 mL) (About 12 g) was added and the mixture was stirred overnight at room temperature under hydrogen at atmospheric pressure. The solid was filtered through celite, washed with methanol and the filtrate was concentrated. The residue was purified by column chromatography (dichloromethane-methanol, 98: 2-&gt; 95: 5) to give the title compound (3.45 g, 90%). m.p. 131 to 132 ° C. (from ethyl acetate-via).

B2. (+/-)-2-Amino-3- (5-ethoxy-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Stirring of (+/-)-3- (5-ethoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester (5.3 g, 17.3 mmol) in anhydrous methanol (50 ml) Raney nickel was added to the resulting solution and the mixture was stirred overnight at room temperature under H ₂ at atmospheric pressure. The reaction mixture was filtered through a pad of celite and the solids were washed with methanol. The filtrate was concentrated and the residue was purified by column chromatography (dichloromethane-methanol, 95: 5) to give (+/-)-2-amino-3- (5-ethoxy-1H-indol-3-yl). 2-Methyl-propionic acid methyl ester (4.2 g, 90%) was obtained as white crystals. mp 165-166 ° C. (from ethyl acetate-hexane).

B3. (+/-)-2-amino-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -2-methyl-propionic acid methyl ester

(+/-)-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -2-methyl-2-nitro-propionic acid methyl ester in anhydrous methanol (200 ml) (12.7) g, 37.8 mmol) was added Raney nickel (about 20 g) and the mixture was stirred overnight at room temperature under H ₂ at atmospheric pressure. The reaction mixture was filtered through a pad of celite and the solids were washed with methanol. The filtrate was concentrated and the residue was purified by column chromatography (dichloromethane-methanol, 9: 1) to give (+/-)-2-amino-3- [5- (2-methoxy-ethoxy)- 1H-indol-3-yl] -2-methyl-propionic acid methyl ester (5.98 g, 52%) was obtained. mp 117-118 ° C. (from ethyl acetate-via).

B4. (+/-)-2-Amino-3- (5-chloro-lH-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m.p .: 170 ℃

B5. (+/-)-2-Amino-3- (5-bromo-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m / z (MH ⁺ ) = 311.0 / 313.0, mp: 181 ° C.

Starting from the appropriate compounds C6 to C10, the following compounds B6 to B10 can be prepared using procedures similar to those achieved for compound B1.

B6. (+/-)-2-amino-2-ethyl-3- (5-methoxy-1 H-indol-3-yl) -propionic acid ethyl ester; MS: m / z (MH ⁺ ) = 291.0

B7. (+/-)-2-Amino-3- (5-ethoxy-1 H-indol-3-yl) -2-ethyl-propionic acid ethyl ester

B8. (+/-)-2-Amino-2-ethyl-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -propionic acid ethyl ester

B9. (+/-)-2-Amino-3- (5-chloro-lH-indol-3-yl) -2-ethyl-propionic acid ethyl ester

B10. (+/-)-2-Amino-3- (5-bromo-1 H-indol-3-yl) -2-ethyl-propionic acid ethyl ester

B11. (RS) -2-Amino-3- (5-cyclopropylmethoxy-1H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m.p. 172 ° C. (dichloromethane-from diesel).

B12. (RS) -2-Amino-3- [5- (1,1-difluoro-methoxy) -1 H-indol-3-yl] -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m.p. 140 to 142 ° C. (from ethyl acetate-via).

B13. (RS) -2-Amino-3- (5-trifluoromethoxy-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound can be prepared similar to the procedure described for compound B1.

Starting from the appropriate compounds C14 to C16, the following compounds B14 to B16 can be prepared using procedures similar to those achieved for compound B1.

B14. (+/-)-2-Amino-3- (5-cyclopropylmethoxy-1 H-indol-3-yl) -2-ethyl-propionic acid ethyl ester

B15. (+/-)-2-amino-3- [5- (1,1-difluoro-methoxy) -1 H-indol-3-yl] -2-ethyl-propionic acid ethyl ester

B16. (+/-)-2-Amino-2-ethyl-3- (5-trifluoromethoxy-1 H-indol-3-yl) -propionic acid ethyl ester

B17. (RS) -2-Amino-2- (5-methoxy-1 H-indol-3-ylmethyl) -3-methyl-butyric acid ethyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. MS: m / z (MH ⁺ ) = 305.0

B18. (RS) -2-Amino-3- (4-fluoro-5-methoxy-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m / z (MH ⁺ ) = 264

B19. (RS) -2-Amino-3- (6-fluoro-5-methoxy-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m / z (MH ⁺ ) = 264

B20. (RS) -2-Amino-3- (5-chloro-6-fluoro-1 H-indol-3-yl) -2-methyl-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared in analogy to the procedure described for compound B1. m / z (MH ⁺ ) = 284.8

C1. (+/-)-3- (5-methoxy-1 H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

A solution of commercial 5-methoxy gramine (6.24 g) and commercial methyl 2-nitro-propionate (4.07 g) in a mixture of toluene (50 ml) and N, N-dimethylformamide (2 ml) was prepared. Argon was bubbled through the reaction mixture for 1 day while bubbling. The solvent was evaporated and the residue was dissolved in dichloromethane (300 ml) and subsequently washed with 2M aqueous HCl, 2M aqueous NaOH and water, dried and concentrated. The residue was purified by column chromatography (toluene-acetone, 98: 2-&gt; 95: 5) to give the title compound (3.42 g, 38%). m.p. 109-110 ° C. (from ethyl acetate-via).

C2. (+/-)-3- (5-ethoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

(5-ethoxy-1H-indol-ylmethyl) -dimethyl-amine (2.18 g, 10 mmol) in anhydrous toluene (17 ml) and commercially available methyl 2-nitro-propionate (1.60 g, 12 mmol, 1.2 Equivalents) was refluxed. When TLC (toluene-acetone, 9: 1) showed that the starting material was extinguished, the mixture was cooled and diluted with chloroform (35 ml). This is subsequently followed by 10% aqueous HCl (2 × 10 ml), water (10 ml), 5% aqueous NaOH (2 × 10 ml), water (10 ml) and 20% aqueous Na ₂ SO ₄ (10 ml). Wash, dry and remove solvent under reduced pressure. The residue was purified by column chromatography (petroleum-ethyl acetate, 4: 1-&gt; 7: 3) to give (+/-)-3- (5-ethoxy-1H-indol-3-yl) -2-methyl- 2-nitro-propionic acid methyl ester (2.07 g, 68%) was obtained as a white solid. mp 80-82 ° C. (from ethyl acetate-hexane).

C3. (+/-)-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -2-methyl-2-nitro-propionic acid methyl ester

(5- (2-methoxy-ethoxy) -1H-indol-ylmethyl) -dimethyl-amine (15.2 g, 61.4 mmol) in a mixture of toluene (100 ml) and N, N-dimethylformamide (50 ml) To the solution of was added methyl 2-nitropropionate (8.5 g, 63.9 mmol). The mixture was refluxed for 2 days with stirring while passing a high velocity stream of argon through the solution. The solvent is evaporated and the residue is dissolved in dichloromethane (600 ml) and subsequently washed with 2 M hydrochloric acid, 2 M aqueous NaOH and water, dried and evaporated. The residue was purified by column chromatography (toluene-acetone, 9: 1) to give (+/-)-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -2- Methyl-2-nitro-propionic acid methyl ester was obtained (9.34 g, 45%).

C4. (+/-)-3- (5-chloro-lH-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound C1.

C5. (+/-)-3- (5-bromo-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound C1.

Starting from ethyl 2-nitrobutyrate and selecting the appropriate amine compounds D1 to D5 as reaction partners, the following compounds C6 to C10 can be prepared using procedures similar to those achieved for compound C1.

C6. (+/-)-2-ethyl-3- (5-methoxy-1H-indol-3-yl) -2-nitro-propionic acid ethyl ester; MS: m / z (MH ⁺ ) = 320.2

C7. (+/-)-3- (5-ethoxy-1H-indol-3-yl) -2-ethyl-2-nitro-propionic acid ethyl ester

C8. (+/-)-2-ethyl-3- [5- (2-methoxy-ethoxy) -1 H-indol-3-yl] -2-nitro-propionic acid ethyl ester

C9. (+/-)-3- (5-chloro-lH-indol-3-yl) -2-ethyl-2-nitro-propionic acid ethyl ester

C10. (+/-)-3- (5-bromo-1H-indol-3-yl) -2-ethyl-2-nitro-propionic acid ethyl ester

C11. (RS) -3- (5-cyclopropylmethoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from compound D6, the title compound was prepared similar to the procedure described for compound C1.

C12. (RS) -3- [5- (1,1-difluoro-methoxy) -1H-indol-3-yl] -2-methyl-2-nitro-propionic acid methyl ester

Starting from compound D7, the title compound was prepared similar to the procedure described for compound C1.

C13. (RS) -3- (5-trifluoromethoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from compound D8, the title compound can be prepared similar to the procedure described for compound C1.

Starting from ethyl 2-nitrobutyrate and selecting the appropriate amine compounds D6 to D8 as reaction partners, the following compounds C14 to C16 can be prepared using procedures similar to those achieved for compound C1.

C14. (+/-)-3- (5-cyclopropylmethoxy-1H-indol-3-yl) -2-ethyl-2-nitro-propionic acid ethyl ester

C15. (+/-)-3- [5- (1,1-difluoro-methoxy) -1 H-indol-3-yl] -2-ethyl-2-nitro-propionic acid ethyl ester

C16. (+/-)-2-ethyl-2-nitro-3- (5-trifluoromethoxy-1H-indol-3-yl) -propionic acid ethyl ester

C17. (RS) -2- (5-methoxy-1H-indol-3-ylmethyl) -3-methyl-2-nitro-butyric acid ethyl ester

Starting from 3-methyl-2-nitro-butyric acid ethyl ester and compound D1, the title compound was prepared similar to the procedure described for compound C1. In this case, 1 equivalent of potassium hydrogen carbonate was added to the reaction mixture. MS: m / z (MH ⁺ ) = 334.9

C18. (RS) -3- (4-fluoro-5-methoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound C1. m / z (MH ⁺ ) = 310.7

C19. (RS) -3- (6-Fluoro-5-methoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound C1. m / z (MH ⁺ ) = 310.6

C20. (RS) -3- (6-chloro-5-methoxy-1H-indol-3-yl) -2-methyl-2-nitro-propionic acid methyl ester

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound C1. m / z (MH ⁺ ) ^- = 313.2

D1. (5-methoxy-1H-indol-3-ylmethyl) -dimethyl-amine

The title compound (5-methoxy-gramine) is commercially available.

D2. (5-ethoxy-1H-indol-3-ylmethyl) -dimethyl-amine

A mixture of 5-ethoxy-indole (7.84 g, 48.7 mmol), 40% aqueous dimethylamine (9.25 ml, 73 mmol, 1.5 equiv) and 96% acetic acid (30 ml) was stirred at 0 ° C. and then 36% form Aqueous aldehyde solution (6.33 ml, 82.7 mmol, 1.7 equiv) was added dropwise. The mixture was allowed to come to room temperature and after stirring overnight, the starting material was extinguished in TLC (dichloromethane-methanol, 4: 1). 10% aqueous NaOH (150 ml) was added and the mixture was stirred at rt for 2 h. Then it was extracted with dichloromethane (4 x 200 ml) and the organic layer was dried and concentrated. The residue was purified by column chromatography (dichloromethane-methanol, 4: 1 → methanol-aqueous ammonia 50: 1) to give the crude product (10.18 g, 96%) which was crystallized from acetone to give pure (5- to Toxy-1H-indol-ylmethyl) -dimethyl-amine (10.2 g, 96%) was obtained as white crystals. m.p. 95 to 97 ° C.

D3. [5- (2-methoxy-ethoxy) -1 H-indol-3-ylmethyl] -dimethyl-amine

A solution of 5- (2-methoxy-ethoxy) -indole (2.06 g, 11.0 mmol) in acetic acid (7 ml) and 40% aqueous dimethylamine (2.1 ml) was cooled to 0 ° C. and 36% aqueous formaldehyde (1.38 ml) (precooled to 0 ° C.) was added dropwise. The mixture was stirred at rt overnight, 2 M hydrochloric acid was added and the mixture was washed with dichloromethane. The aqueous layer was alkalized with 10% NaOH and extracted with dichloromethane. The combined organic layers were washed with water, dried and concentrated. The residue was purified by column chromatography (dichloromethane-methanol, 4: 1-&gt; dichloromethane-methanol-water-aqueous ammonia, 10: 20: 1: 1) to give [5- (2-methoxy-ethoxy)- 1H-indol-ylmethyl] -dimethyl-amine (2.42 g, 90%) was obtained. m.p. 163 to 164 ° C. (from toluene-N, N-dimethylformamide).

D4. (5-Chloro-1H-indol-3-ylmethyl) -dimethyl-amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3. m.p .: 127 to 130 ° C

D5. (5-Bromo-1H-indol-3-ylmethyl) -dimethyl-amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3. m.p .: 139 ° C

D6. (5-cyclopropylmethoxy-1H-indol-3-ylmethyl) -dimethyl amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3.

D7. [5- (1,1-Difluoro-methoxy) -1 H-indol-3-ylmethyl] -dimethyl amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3.

D8. [5-Trifluoromethoxy-1H-indol-3-ylmethyl] -dimethyl amine

Starting from the appropriate starting compound, the title compound can be prepared similar to the procedure described for compound D2 or D3.

D9. (4-Fluoro-5-methoxy-1H-indol-3-ylmethyl) -dimethyl amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3. m / z (MH ⁺ ) = 222.8

D10. (6-Fluoro-5-methoxy-1H-indol-3-ylmethyl) -dimethyl amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3. m / z (MH ⁺ ) = 222.6

D11. (5-Chloro-5-fluoro-1 H-indol-3-ylmethyl) -dimethyl amine

Starting from the appropriate starting compound, the title compound was prepared similar to the procedure described for compound D2 or D3. m / z (MH ⁺ ) = 226.8

E1. 5-ethoxy-indole

A mixture of commercially available 5-hydroxy-indole (18 g, 13.5 mmol), anhydrous K ₂ CO ₃ (93.5 g, 5 equiv) and iodoethane (40.5 ml, 3.75 equiv) in acetone (180 mL) under argon Stir at 50 ° C. When disappearance of 5-hydroxy-indole in TLC (dichloromethane-methanol, 95: 5) (4 days), the mixture was filtered, the solids were washed with acetone and the filtrate was concentrated to 17.67 g (90 %) Of the title compound was obtained, which was pure enough to be used in the next step. mp 144-146 ° C. (from ethanol).

E2. 5- (2-methoxy-ethoxy) -1 H-indole

To a solution of 5-hydroxy-indole (15.2 g, 114 mmol) in 250 ml of anhydrous acetone, 2-methoxyethyl iodide (15 ml, 141 mmol, 1.25 equiv) and anhydrous K ₂ CO ₃ (46.7 g, 338 mmol, 3 equiv) was added and the mixture was refluxed. Additional 0.5 equivalents of 2-methoxyethyl iodide and K ₂ CO ₃ were added to each primary. After 6 days, TLC (toluene-acetone, 9: 1) showed that the starting material disappeared. The solid was removed by filtration and the solvent was evaporated. The residue was dissolved in dichloromethane (800 ml) and the solution was washed with 2 M aqueous HCl, 10% aqueous NaHCO ₃ and water. The organic layer was dried and concentrated. Purification by column chromatography (toluene-acetone, 9: 1) afforded 5- (2-methoxy-ethoxy) -1H-indole (18.8 g, 86%). mp 58-60 ° C. (from ethyl acetate-via).

E3. 5-chloro-1H-indole

The title compound is commercially available.

E4. 5-bromo-1H-indole

The title compound is commercially available.

E5. 5-cyclopropylmethoxy-1H-indole

To a solution of 7.3 g of 5-hydroxy-indole in 130 ml of anhydrous acetone was added 10.5 ml of bromomethyl cyclopropane and 22.7 g of anhydrous potassium carbonate. The mixture was heated to reflux for 24 h and an additional amount of 5 ml bromomethyl cyclopropane was added. The mixture was heated to reflux for an additional 4 days. The mixture is filtered and the solvent is removed under reduced pressure. The residue was dissolved in dichloromethane and washed with aqueous hydrochloric acid solution (2 M), 10% aqueous NaHCO ₃ and water. The organic layer was dried and the solvent was removed under reduced pressure. After purification by column chromatography (silica gel; toluene, acetone 95: 5), the title compound (9.62 g, 94%) was obtained as an oil.

E6. 5- (1,1-Difluoro-methoxy) -1 H-indole

Chlorodifluoromethane was ice cooled with 6.65 g of 5-hydroxy-indole and 3.69 g of tetrabutylammonium iodide in a mixture (50%) of 70 ml of dioxane and 20 ml of sodium hydroxide Bubble through the solution. After disappearance of the starting material in TLC, 500 ml of dichloromethane were added. The mixture was washed with water. The organic layer was dried and the solvent was removed under reduced pressure. After purification by column chromatography (silica gel; toluene, acetone 99: 1), 2.19 g (24%) of the title compound were obtained as a colorless liquid.

E7. 5-trifluoromethoxy-1H-indole

The title compound can be obtained from 5-hydroxy-1H-indole by trifluoromethylation reaction.

E8. 6-fluoro-5-methoxy-1H-indole and

E9. 4-fluoro-5-methoxy-1H-indole

The two title compounds were prepared similar to the procedure described in WO 2003/064413 (p. 91f) for the preparation of 4-fluoro-5-methoxyindole and 6-fluoro-5-methoxyindole as a mixture. In this case, the regioisomeric intermediates (4-fluoro-5-methoxy-2-nitro-phenyl) -acetonitrile and (2-fluoro-3-methoxy-6-nitro-phenyl) -acetonitrile Crystallization of (4-fluoro-5-methoxy-2-nitro-phenyl) -acetonitrile from a series of 2-propanol using the mother liquor of previous crystallization (m / z (MH ⁺ ) = 166.1), followed by Separation by crystallization of (2-fluoro-3-methoxy-6-nitro-phenyl) -acetonitrile (m / z (MH ⁺ ) = 166.1) from toluene.

E10. 5-chloro-6-fluoro-1H-indole

To a suspension of 12.4 g of sodium 1-acetyl-6-fluoro-1H-indole-2-sulfonate in 30 ml of acetonitrile was added 7.1 g of N-chlorosuccinimide. The mixture was stirred for 2 hours at room temperature and heated to 110 ° C. 450 ml of aqueous sodium hydroxide solution (1 M) was added. The solution was stirred at 110 ° C. for 1 hour and cooled to 0 ° C. The organic layer was separated and the solvent removed. After the residue was purified by column chromatography (heptane / methyl tert-butyl ether), 7.82 g (39%) of the title compound were obtained. m / z (MH ⁺ ) ^- = 168.0

F1. 2-methoxyethyl iodide

The crude 2-methoxyethyl tosylate was dissolved in 1600 ml of acetone and NaI (300 g, 2 mol, 2 equiv) was added. The mixture was heated to reflux and the progress of the reaction was monitored by TLC (toluene-acetone, 9: 1). After 3 hours, the mixture was cooled to room temperature and the solids were removed by filtration. The solvent was evaporated and the residue was dissolved in dichloromethane (700 ml) and washed with 10% aqueous Na ₂ S ₂ O ₃ and water. The organic layer was dried and the solvent was evaporated. The residue was distilled off under reduced pressure to give 108 g (58%) of 2-methoxyethyl iodide. bp 34 to 36 ° C. (30 mbar).

G1. Toluene-4-sulfonic acid 2-methoxy-ethyl ester

A slurry of p-toluenesulfonyl chloride (205 g, 1.08 mol) and pyridine (150 mL) was stirred under argon atmosphere. While maintaining the temperature below 5 ° C. (ice-water bath), ethylene glycol monomethyl ether (80 ml, 1 mol) was added slowly from the dropping funnel. After the addition was complete, the mixture was stirred under 5 ° C. for 1 hour. The mixture was poured into ice water (1 L) and extracted with dichloromethane (1.2 L). The organic layer was washed with ice cold 6 M HCl (3 × 350 ml) and reduced to minimum volume by evaporation in vacuo.

H1. 3-methyl-2-nitro-butyric acid ethyl ester

In an ice cooled solution of 5.31 g of sodium nitrite and 8 g of dried phloroglucinol in 70 ml of dimethyl formamide, 11.3 g of 2-iodo-3-methyl in 30 ml of dimethyl formamide A solution of butyric acid ethyl ester was added. The solution was allowed to warm to room temperature and stirred overnight. The solvent was removed at reduced pressure. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried and the solvent was removed. The title compound was obtained as an oil. MS: m / z (M ⁺ ) = 176.1

I1. 2-iodo-3-methyl-butyric acid ethyl ester

A mixture of 10 g of commercial ethyl-2-bromo isovalerate and 17.8 g of sodium iodide in 150 ml of acetone was heated to reflux overnight. The solvent was removed under reduced pressure. Dichloromethane was added to the residue and the solution was washed with aqueous sodium thiosulfate solution (10%) and brine. The organic layer was dried and the solvent was removed under reduced pressure. 11.34 g (93%) of the title compound were obtained as a yellow oil. MS: m / z (M ⁺ ) = 255.9

J1. Sodium 1-acetyl-6-fluoro-1 H-indole-2-sulfonate

A mixture of 14.0 g 6-fluoro-1H-indole-2-sulfonate and 87 ml of acetic anhydride was stirred at 70 ° C. for 20 minutes. 35 ml of additional acetic anhydride was added and the temperature was maintained at 70 ° C. for 17 minutes. An additional 46 ml of acetic anhydride was added and the temperature raised to 110 ° C. After 1 hour, the temperature was lowered to 90 ° C. for an additional 90 minutes. After cooling to room temperature, 180 ml of diethyl ether were added. The precipitate was filtered off and dried under reduced pressure. 12.5 g (76%) of the title compound were obtained as a colorless solid. m / z (MH ⁺ ) ^- = 258

K1. Sodium 6-Fluoro-1H-indole-2-sulfonate

To a solution of 23.4 g sodium bisulfite in 80 ml of water was added dropwise a solution of 13.5 g of 6-fluoro indole in ethanol. The resulting suspension was stirred overnight at room temperature. The precipitate was filtered off and washed with cold water, cold methanol and diethyl ether. 7.0 g (29%) of the title compound were obtained as a colorless solid.

Commercial usability

The compounds according to the invention have valuable pharmacological properties which can make them commercially available. Thus, for example, the compounds according to the invention may act as inhibitors of mitotic kinesin Eg5, and these compounds are expected to be commercially available for the treatment of diseases reactive to the inhibition of kinesin, such as the diseases mentioned below. . Furthermore, for example, the compounds according to the invention may exhibit cell-cycle dependent, antiproliferative and / or apoptosis inducing activity.

Mitotic kinesin Eg5 is an enzyme essential for the assembly and function of bipolar mitotic spindles. Eg5 plays an essential role during the various stages of mitosis. Drugs that alter mitosis have been demonstrated to be clinically effective in the treatment of numerous cancers. Despite the various arrays of essential spindle proteins that can be used as targets for the discovery of new cancer therapies, all spindle-targeted therapeutic agents in today's clinical applications are only on one protein, tubulin Works. Surprisingly, kinesin Eg5 expression is most abundant in proliferating human tissue, whereas most postmitotic cells, such as human central nervous system neurons, are consistent with the exclusive or nearly limited role of Eg5 in cell proliferation. In contrast to drugs that directly interfere with microtubule dynamic instability, Eg5 kinesin inhibitors are expected not to disrupt microtubule-based cellular processes that are not involved in proliferation, such as neuronal transport. During mitosis, Eg5 is essentially involved in organizing the microtubules into bipolar structures that form mitotic spindles. Experimental fluctuations in Eg5 function lead to characteristic malformations or dysfunction of mitotic spindles, often leading to cell cycle arrest and cell death.

The compounds according to the invention can be used to regulate mitotic spindle formation, thus leading to prolongation of cell cycle arrest in mitosis, often leading to apoptosis. By “modulate” herein is meant to change mitotic spindle formation, including increasing and decreasing spindle formation. By “mitotic spindle formation” is meant herein the organization of microtubules into bipolar structures by mitotic kinesins. "Dysfunction of mitotic spindle" as used herein means mitotic arrest and unipolar spindle formation. "Horbites of mitotic spindle" include splay of mitotic spindle poles, or otherwise resulting in morphological fluctuations of the mitotic spindle.

In addition, the compounds may be useful for the treatment of benign or malignant neoplasms.

A "neoplasm" is defined as a cell that exhibits blocking of abnormal cell proliferation and / or survival, and / or differentiation. A "benign neoplasm" is described as a hyperproliferation of cells that are unable to form tumors in vivo that metastasize aggressively. In contrast, “malignant neoplasms” are described as cells with multiple neoplastic and biochemical abnormalities that can form systemic diseases, such as tumor metastasis in distant organs.

Various diseases are caused by abnormal cell proliferation (“hyperproliferation”), and avoidance from apoptosis. These diseases include, for example, benign hyperplasia of prostate ("BPH") or colon epithelial tissue, psoriasis, glomerulonephritis or osteoarthritis. Most importantly, these diseases include malignant neoplasms commonly described as cancer and are characterized by tumor cells that eventually metastasize to distant organs or tissues. Malignant neoplasms include solid and hematological tumors. Solid tumors include the breast, bladder, bone, brain, central and peripheral nervous system, colon, endocrine glands (eg, thyroid and adrenal cortex), esophagus, endometrium, germ cells, head and neck, kidneys, liver, lungs, Laryngeal and hypopharyngeal, mesothelioma, sarcoma, ovary, pancreas, prostate, rectum, renal, small intestine, soft tissue, testes, stomach, skin, ureters, vagina and vulva. Malignant neoplasms include hereditary cancers exemplified by retinoblastoma and Wilms' tumor. Malignant neoplasms also include primary tumors in these organs, and corresponding secondary tumors in distant organs (“tumor metastasis”). Hematological tumors are aggressive and painless forms of leukemia and lymphoma, namely non-Hodgkin's disease, chronic and acute myeloid leukemia (CML / AML), acute lymphocytic leukemia (ALL), Hodgkin's disease, multiple myeloma And T-cell lymphoma. Also included are myelodysplastic syndromes, plasma cell neoplasia, paraneoplastic syndromes, cancers of unknown primary sites and AIDS related malignancies.

It should be noted that cancer diseases and malignant neoplasms do not necessarily require the formation of metastases in distant organs. Certain tumors exert their effects on devastating the primary organs themselves through their aggressive growth properties. They can eventually cause loss of designated organ function, leading to destruction of tissue and organ structure.

Neoplastic cell proliferation can affect normal cell behavior and organ function. For example, the formation of new blood vessels, a process described as angiogenesis, is induced by tumors or tumor metastasis. The compounds according to the invention may be commercially available for the treatment of pathophysiologically related processes caused by benign or neoplastic cell proliferation, including but not limited to angiogenesis by non-physiological proliferation of vascular endothelial cells. have.

Drug resistance is a particularly important part of the frequent failure of standard cancer therapies. Such drug resistance is caused by various cellular and molecular mechanisms such as drug outflow pumps or overexpression of mutations in cell target proteins. The commercial availability of the compounds according to the invention is not limited to the first line treatment of patients. Patients with resistance to defined cancer chemotherapy or target specific anticancer drugs (second or third line treatment) may also be adapted to treatment with the compounds according to the invention.

Due to their cellular antiproliferative properties, the compounds according to the invention can also be used in addition to diseases related to cell cycle and cell proliferation, such as cancers discussed above, for example fibrotic and differentiation disorders, psoriasis, rheumatoid arthritis, atherosclerosis It may also be commercially available for the treatment of sclerosis, hyperplasia, restenosis, cardiac hypertrophy, (auto) immune disorders, fungal disorders, bone disease, or acute or chronic inflammation.

The compounds according to the invention can be used for the treatment, prevention or amelioration of diseases of the benign and malignant behavior described above, for example benign or malignant neoplasms, especially cancers (such as any cancer disease described above), in particular those susceptible to inhibition of Eg5. It may be commercially available for.

Depending on their properties, functions and ease of use referred to herein, the compounds according to the invention have valuable and desirable effects in relation to them, such as low toxicity, generally good bioavailability (such as good digestive tract absorption), good therapeutic range It is expected to be characterized by the absence of significant side effects, and / or additional beneficial effects with respect to their therapeutic and pharmaceutical suitability.

The present invention further provides pharmacologically active and therapeutically effective methods for treating (over) proliferative diseases and / or disorders responsive to the induction of apoptosis, particularly mammals including humans in need of treatment for the above-mentioned diseases, disorders, symptoms or diseases. (E) hyperproliferative diseases and / or disorders responsive to the induction of apoptosis, in particular administering an effective and tolerable amount of one or more compounds according to the invention, in particular the diseases, disorders, symptoms or diseases mentioned above Methods of treating mammals, including humans suffering from.

The invention further comprises administering to a subject in need of therapy for a benign or malignant neoplastic disease, such as cancer, a pharmacologically active, therapeutically effective and tolerable amount of one or more compounds according to the invention. Methods useful for regulating apoptosis and / or abnormal cell growth in the treatment of malignant neoplastic diseases such as cancer.

The invention further comprises administering to the patient in need of modulating, in particular inhibiting, Eg5 activity in the cell, a pharmacologically active, therapeutically effective and tolerable amount of one or more compounds according to the invention. Methods of modulating, in particular, inhibiting activity.

The present invention further provides mitotic spindle formation, including regulation of mitotic spindles, ie, reduction of spindle formation, or an increase or decrease in spindle pole separation that causes malformations of the mitotic spindle pole. Control of mitotic spindles, i.e., of spindle formation, comprising administering to a patient in need thereof a pharmacologically active, therapeutically effective and acceptable amount of one or more compounds according to the invention. A method of changing mitotic spindle formation is provided, including a decrease or an increase or decrease in spindle pole separation that causes malformation of the mitotic spindle pole.

The invention further comprises administering to a patient in need of inhibition of mitosis in a cell a pharmacologically active, therapeutically effective and tolerable amount of one or more compounds according to the invention to inhibit mitosis in the cell. It includes a method.

The invention further relates to the treatment of (hyper) proliferative diseases and / or disorders, eg, benign or malignant neoplasms such as cancer, which are responsive to the induction of diseases and / or disorders associated with Eg5 kinesin activity, eg apoptosis, Diseases and / or disorders associated with Eg5 kinesin activity in a mammal, comprising administering to the mammal in need thereof a pharmacologically active, therapeutically effective and tolerable amount of one or more compounds according to the invention, For example, methods of treating, preventing or ameliorating (hyper) proliferative diseases and / or disorders, such as benign or malignant neoplasms such as cancer, which are responsive to the induction of apoptosis.

The invention further relates to the use of the compounds according to the invention for the preparation of pharmaceutical compositions which are used for the treatment, prevention and / or amelioration of one or more of the mentioned diseases.

The invention may further be used for the treatment, prevention or amelioration of (hyper) proliferative diseases and / or disorders of benign or malignant behavior, for example benign or malignant neoplasms such as cancer, which are responsive to the induction of apoptosis in mammals. To a use of a compound according to the invention for the preparation of a pharmaceutical composition.

The invention further relates to the use of a compound according to the invention for the preparation of a pharmaceutical composition which can be used for the treatment, prevention or amelioration of disorders reactive to the arrest of aberrant cell growth and / or induction of apoptosis.

The invention further relates to the use of the compounds according to the invention for the preparation of pharmaceutical compositions for the treatment, prevention or amelioration of benign or malignant neoplasms, in particular cancer, such as any of the cancer diseases described above.

The invention further relates to a pharmaceutical composition comprising at least one compound according to the invention and a pharmaceutically acceptable carrier or diluent.

The invention further relates to pharmaceutical compositions prepared by combining at least one compound according to the invention with a pharmaceutically acceptable carrier or diluent.

The invention further relates to a pharmaceutical composition comprising at least one compound according to the invention and a pharmaceutically acceptable adjuvant and / or excipient.

The invention further provides one or more compounds according to the invention and pharmaceutically acceptable auxiliaries, excipients, for example for the treatment, prevention or amelioration of benign or malignant neoplasms, in particular cancer, such as any of the cancer diseases described above. And / or a combination comprising a vehicle.

The present invention further provides compounds and pharmaceutically acceptable excipients, carriers and / or according to the invention, for example for the treatment, prevention or amelioration of benign or malignant neoplasms, especially cancer, such as any of the cancer diseases described above. It relates to a combination comprising a diluent.

The invention further provides a conventional pharmaceutically acceptable vehicle for use in therapy, for example for the treatment, prevention or amelioration of a hyperproliferative disease, for example cancer, and / or a disorder responsive to the induction of apoptosis, A composition consisting essentially of a therapeutically effective tolerable amount of at least one compound according to the invention in combination with a diluent and / or excipient.

The present invention further relates to therapies in the treatment of (positive) proliferative diseases and / or disorders of positive or malignant behavior, for example responsive to the induction of apoptosis, such as the diseases mentioned herein, in particular cancer. It relates to a compound according to the invention for use.

The invention further relates to a compound according to the invention having antiproliferative and / or apoptosis inducing activity.

The invention further relates to the compounds according to the invention having Eg5 inhibition properties.

The invention further relates to a pharmaceutical composition according to the invention having Eg5 inhibitory properties.

The invention further relates to a pharmaceutical composition according to the invention having antiproliferative activity.

The invention further relates to a pharmaceutical composition according to the invention having apoptosis inducing activity.

The invention further comprises a pharmaceutical composition comprising at least one compound according to the invention and a pharmaceutically acceptable carrier or diluent as the sole active ingredient (s) in the manufacture of a medicament for the treatment and / or prophylaxis of the abovementioned diseases. It relates to the use of.

Further, the present invention relates to an article of manufacture comprising a packaging material and a medicament contained in the packaging material, wherein the medicament comprises: inhibition of Eg5 and / or inhibition of cell (hyper) proliferation and / or induction of apoptosis, It is therapeutically effective to ameliorate signs of (hyper) proliferative diseases and / or disorders that are responsive to the induction of Eg5-mediated diseases and / or apoptosis, wherein the packaging agent is responsive to the induction of Eg5-mediated diseases and / or apoptosis. A label or package insert is indicated that is useful for preventing or treating phosphorus (hyper) proliferative diseases and / or disorders, wherein the medicament comprises one or more compounds according to the invention. Packaging materials, labels and package inserts are otherwise comparable to or similar to those generally considered as standard packaging materials, labels and package inserts for medicaments with relevant utility.

Pharmaceutical compositions according to the invention are prepared by methods known and well known to those skilled in the art. As pharmaceutical compositions, the compounds of the invention (= active compounds) are themselves or preferably in combination with suitable pharmaceutical auxiliaries and / or excipients, for example tablets, coated tablets, dragees, pills, cachets, Granules, capsules, caplets, suppositories, patches (eg, as TTS), emulsions (such as micro-emulsions or lipid emulsions), suspensions (such as nanosuspensions), gels, solvates or solutions (e.g., For example, in the form of sterile solutions) or encapsulated in liposomes, or used as a complex comprising beta-cyclodextrin or beta-cyclodextrin derivatives, etc., the active compound content is advantageously 0.1 to 95%, wherein the adjuvant and / or By appropriate choice of excipients, pharmaceutical dosage forms (eg, delayed release or enteric forms) that are precisely adapted to the desired initiation of the active compound and / or action can be achieved.

Those skilled in the art will, due to their expertise, be familiar with adjuvants, vehicles, excipients, diluents, carriers or adjuvants suitable for the desired pharmaceutical formulation, formulation or composition. In addition to solvents, gel formers, ointment bases and other active compound excipients, for example, antioxidants, dispersants, emulsifiers, preservatives, solubilizers (such as polyoxyethyleneglyceroltriricinoleate 35, PEG 400, Tween 80 , Captisol, Solutol HS15, etc.), colorants, complexing agents, permeation accelerators, stabilizers, fillers, binders, thickeners, disintegrants, buffers, pH adjusting agents (e.g. neutral, alkaline or acidic) To obtain a formulation), polymers, lubricants, coatings, propellants, tonicity modifiers, surfactants, flavors, sweeteners or dyes can be used.

In particular, any type of adjuvant and / or excipient suitable for the desired formulation and desired mode of administration is used.

Administration of the compounds, pharmaceutical compositions, or combinations according to the invention can be carried out in any of the commonly accepted modes of administration available in the art. Examples of suitable modes of administration include intravenous, oral, intranasal, parenteral, topical, transdermal and rectal administration. Oral and intravenous administration is preferred.

For the treatment of skin diseases, the compounds of the present invention may be administered in the form of pharmaceutical compositions which are particularly suitable for topical application. For the preparation of pharmaceutical compositions, the compounds of the present invention (= active compound) are preferably mixed with suitable pharmaceutical auxiliaries and further processed to provide suitable pharmaceutical formulations. Suitable pharmaceutical formulations are, for example, powders, emulsions, suspensions, sprays, oils, ointments, fatty ointments, creams, lotions, pastes, gels or solutions.

Pharmaceutical compositions according to the invention can be prepared by known methods. Dosages of the compounds of the invention (= active compound) are in the usual range for Eg5 inhibitors, inhibitors for cell (hyper) proliferation or apoptosis inducers. Topical application forms (such as ointments) for the treatment of skin diseases thus contain the active compound, for example at a concentration of 0.1 to 99%. Typical doses in the case of systemic therapy (p.o.) may be 0.03 to 60 mg / kg per day, and in case of (i.v.) they may be 0.03 to 60 mg / kg per hour. In other embodiments, typical dosages for systemic therapy (p.o.) are 0.3 to 30 mg / kg per day, and (i.v.) for 0.3 to 30 mg / kg per hour.

The choice of optimal dosage regimen and dosing duration, in particular the optimal dosage and mode of administration of the active compound required in each case, can be determined by those skilled in the art based on their expertise.

Depending on the particular disease being treated or prevented, additional therapeutically active agents conventionally administered to treat or prevent the disease may optionally be co-administered with the compounds according to the invention. As used herein, additional therapeutic agents commonly administered to treat or prevent certain diseases are known to be appropriate for the disease being treated.

For example, the compounds according to the invention can be combined with one or more standard therapies for use in the treatment of the diseases mentioned above.

In one particular embodiment, the compounds according to the invention can be combined with one or more anticancer agents known in the art, for example one or more chemotherapy and / or target specific anticancer agents described below.

Examples of known chemotherapeutic anti-cancer agents frequently used in combination therapy include (i) Cyclophosphamid (endoxic acid, trademark), Ifosfamid (holoxane, trademark), Thiotepa Alkylating agents / carbamylating agents such as (thiotepa rederle®), Melphalan (alkeran®) or chloroethylnitrosourea (BCNU); (ii) platinum derivatives such as cisplatin (Platinex® BMS), oxaliplatin, satraplatin and carboplatin (Carbroplatt® BMS); (iii) taxanes, such as vinca alkaloids (vincristine, vinblastine, vinorelbine), Paclitaxel (Taxol, ®), docetaxel (Taxote, ®) and analogs, and new formulations thereof and Conjugates (such as Abraxane® with paclitaxel bound to nanoparticle formulation albumin), Epothilone B (Patuphilone®), Azaepothilone (Ixabepilone Mitosis inhibitors / tubulin inhibitors, including epothilones, such as ZK-EPO (fully synthesized epothilone B analogs); (iv) anthracyclines (Doxorubicin / adrivblastin®), epipodophyllotoxins (Etoposide / Etopophos®), and camptothecins and camptothecin analogs (irinotecan) Topoisomerase inhibitors such as Irinotecan / camptosar® or Topotecan / hicampin®; (v) 5-Fluorouracil (5-FU), Capecitabine (Xceloda, registered trademark), Arabinosylcytosine / Cytarabin (Alexan, registered trademark) or gemcitabine Pyrimidine antagonists such as Gemcitabine® (gemzar, registered trademark); (vi) purine antagonists such as 6-mercaptopurine (purie-netol®), 6-thioguanine or fludarabine (fludara®); And (vii) folate antagonists such as methotrexate (Parmitrexate®) and pemetrexed (Alimta®).

Examples of target specific anticancer drug groups used in experimental or standard cancer therapies include (i) Imatinib (Gleevec®), ZD-1839 / Gefitinib (Iresa®) , BAY43-9006 (Sorafenib, Nexavar, Trademark), SU11248 / Sunitinib (Sutent, Trademark), OSI-774 / Erlotinib (Tarceba, Registration Trademarks), Dasatinib (Sprisel, Trademark), Lapatinib (Tikerb, Trademark), and also Batalanib, Vandetanib (Jaktimima) , Kinase inhibitors such as Pazopanib) or Pazopanib; (ii) proteasome inhibitors such as PS-341 / Bortezomib (Velkade, ®); (iii) SAHA (sleeping person, registered trademark), PXD101, MS275, MGCD0103, Depsipeptide / FK228, NVP-LBH589, NVP-LAQ824, Valproic Acid (VPA), CRA / PCI 24781, ITF2357, SB939 and Histone deacetylase inhibitors such as butyrate; (iv) heat shock protein 90 inhibitors such as 17-allylaminogeldanamycin (17-AAG) or 17-dimethylaminogeldanamycin (17-DMAG); (v) VEGF antibodies, such as combretastatin A4 phosphate or AVE8062 / AC7700, and VEGF antibodies such as Bevacizumab (Avastin®) or PTK787 / ZK222584 (Vatalanib) ) Or antiangiogenic drugs, including KDR tyrosine kinase inhibitors such as Vandetanib (Zakthyma®) or Pazopanib; (vi) Trastuzumab (Herceptin, Trademark), Rituximab (MabThera / Rituxan, Trademark), Alemtuzumab (Campas, Trademark) , Tositumomab (Bexar, registered trademark), C225 / Cetuximab (Herbitux, registered trademark), Avastin (see above) or Panitumumab (Vectibix, registered trademark) Monoclonal antibodies, and mutants and conjugates of monoclonal antibodies, such as, for example, Gemtuzumab ozogamicin (Miltartag®) or Ibritumomab tiuxetan ) (Zevalin®) and antibody fragments; (vii) oligonucleotide-based therapeutics such as G-3139 / Oblimersen (Genenass®) or DNMT1 inhibitor MG98; (viii) Toll-like receptor / TLR 9 agonists such as Promune®, TLR 7 agonists such as Imiquimod (Aldara®) or Isatoribine and Analogs thereof, or TLR 7/8 agonists such as Resiquimod, and immunostimulatory RNAs as TLR 7/8 agonists; (ix) protease inhibitors; (x) antiestrogens (e.g. Tamoxifen or Raloxifen), antiandrogens (e.g. Flutamide or Casodex), LHRH analogues (e.g. loops Hormone treatments such as, but not limited to, Luprolide, Goserelin or Triptorelin, and aromatase inhibitors.

Other known target specific anticancer agents that can be used in combination therapy include bleomycin; Retinoids such as all-trans retinoic acid (ATRA); DNA methyltransferase inhibitors such as 5-aza-2'-deoxycytidine (Decitabine, Dacogen®) and 5-azacytidine; Alanosine; Cytokines such as interleukin-2; Interferons such as interferon a2 or interferon-γ; And killing receptor agonists such as TRAIL, DR4 / 5 agonist antibodies, FasL and TNF-R agonists (eg, TRAIL receptor agonist like mapatumumab or lexatumumab).

As exemplary anticancer agents that may be useful in the combination therapy according to the present invention, any of the following drugs may be mentioned without limitation:

5 FU, Actinomycin D, Abarelix, Abkhazimab, Aclarubicin, Adapalene, Alemtuzumab, Altretamine, Aminoglutetimide, Amirylose, Amrubicin, Anastrozole, Annecy Tabine, Artemisinin, Azathioprine, Basiliximab, Bendamustine, Bevacizumab, Bexsar, Bicalutamide, Bleomycin, Bortezomib, Broxuridine, Busulfan, Campas, Caffecitabine , Carboplatin, carbocuone, carmustine, serlorex, chlorambucil, chlormethine, cisplatin, cladribine, clomiphene, cyclophosphamide, dacarbazine, daclizumab, dactinomycin, da Satinib, daunorubicin, decitabine, deslorelline, dexrazoic acid, docetaxel, doxyfluridine, doxorubicin, droloxifene, drostanolone, edelfosin, eflornithine, emitepur, epirubicin, Epithiostanol, eftaplatin, erbitux, erol Rotinib, esturamustine, etoposide, exemestane, padrosol, finasteride, phloxuridine, flucytosine, fludarabine, fluorouracil, flutamide, formemstan, poscarnet ), Phosphestrol, fortemustine, fulvestrant, gefitinib, genasense, gemcitabine, gleevec, goserelin, gospermus, herceptin, idarubicin, idoxuridine, ifosfamide, forehead Tinib, Improsulfan, Infliximab, Irinotecan, Ixabepilone, Llanoretide, Lapatinib, Letrozole, Leproproline, Lovaplatin, Romustine, Lupolilide, Melphalan, Mercaptopurine, Methotrexate, meturedepa, miboplatin, mifepristone, mittefosine, myrimostim, mitoguazone, mitolactol, mitomycin, mitoxantrone, mizoribin, motexapine, milotarg, nartograstim , Nevazumab, Nedaplatin, Nilutamide, Nimu Stain, Octreotide, Ormeloxyphene, Oxaliplatin, Paclitaxel, Palivizumab, Panitumumab, Patupilone, Pazopanib, Pegaspargase, Pegfilgrastim, Pemetrexed, Pentetreo Tide, pentostatin, PERFOSFAMIDE, pifosulfane, pyrarubicin, plicamycin prednisostin, procarbazine, propagernium, propidium chloride, raloxifene, raltitrexed, rannimustine, lan RANPIRNASE, RASBURICASE, LASOXIC acid, Rituximab, Rifampicin, Ritrosulfane, Lomurted, Luboxisturin, Sargramostim, Satraplatin, Sirolimus, Sobuic Acid , Sorafenib, spiromostin, streptozosin, sunitinib, tamoxifen, tasornermine, tegapur, temophorpine, temozolomide, teniposide, testosterone, thiotepa, thimalfasin (THYMALFASIN), Thiamiprine, Topo Cannes, toremifene, TRAIL, trastuzumab, treosulfan, triazcuon, trimetrexate, triphtholin, trophosamide, uredepa, balubisin, batalanib, vandetanib, butteporpin ( VERTEPORFIN), vinblastine, vincristine, vindesine, vinorelbine, borosol and zebarin.

The anticancer agents referred to herein above as combination partners of the compounds according to the invention mean to include pharmaceutically acceptable derivatives thereof, for example pharmaceutically acceptable salts thereof.

Those skilled in the art will know based on their expertise with respect to the type of additional therapeutic agent (s), total daily dosage (s) and dosage form (s) coadministered. The total daily dose (s) may vary over a wide range.

In practicing the present invention, the compounds according to the invention are carried out sequentially, separately from one or more standard therapeutic agents (chemotherapy and / or target specific anticancer agents), in particular anticancer agents known in the art, such as any of those mentioned above. , Concurrently, chronologically staggered, or in combination therapy (eg, combined unit dosage form, separate unit dosage form, adjacent discrete unit dosage form, fixed or non- chronologically staggered). As fixed combinations, kit-of-parts or mixtures).

Accordingly, the present invention further provides for the use of staggered use separately, sequentially, simultaneously, jointly or chronologically in therapy, such as in the treatment of any of the diseases mentioned herein.

A first active ingredient which is at least one compound according to the invention, and

A combination comprising at least one anticancer agent known in the art, such as at least one second active ingredient which is mentioned above.

The term "combination" according to the invention may exist as a kit consisting of a fixed combination, a non-fixed combination or parts.

A “fixed combination” is defined as a combination in which the first active ingredient and the second active ingredient are present together in one unit dose or in a single entity. One example of a "fixed combination" is a pharmaceutical composition in which the first active ingredient and the second active ingredient are present in a mixture for simultaneous administration, such as one formulation. Another example of a “fixed combination” is a pharmaceutical combination wherein the first active ingredient and the second active ingredient are present in one unit rather than in a mixture.

A "kit of parts" is defined as a combination wherein the first active ingredient and the second active ingredient are present in two or more units. One example of a “kit of parts” is a combination in which the first active ingredient and the second active ingredient are present separately. The components of the kit consisting of the parts can be administered separately, sequentially, simultaneously, jointly or chronologically.

The present invention further provides for use in staggered use separately from the therapy, sequentially, simultaneously, jointly or chronologically.

A first active ingredient which is at least one compound according to the invention, and

One or more anticancer agents known in the art, such as one or more second active ingredients which are those mentioned hereinabove, and optionally

It relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent.

The present invention further

a.) at least one compound according to the invention formulated with a pharmaceutically acceptable carrier or diluent, and

b.) A combination product comprising a pharmaceutically acceptable carrier or diluent and at least one anticancer agent known in the art, such as at least one of those mentioned hereinabove.

The invention further comprises the preparation of a first active ingredient, a compound according to the invention, and a pharmaceutically acceptable carrier or diluent, for staggered use simultaneously, jointly, sequentially, separately or chronologically in therapy; And a kit comprising anticancer agents known in the art, such as a second active ingredient which is one of those mentioned above, and a formulation of a pharmaceutically acceptable carrier or diluent. Optionally, the kit includes instructions for its use in therapy to treat (hyper) proliferative diseases and / or disorders, such as cancer, more precisely any cancer disease described above, for example, that are responsive to the induction of apoptosis. do.

The present invention further relates to a combination formulation comprising at least one compound according to the invention for simultaneous, simultaneous, sequential or separate administration and at least one anticancer agent known in the art.

The invention further relates to the combinations, compositions, formulations, preparations or kits according to the invention having Eg5 inhibitory activity and / or antiproliferative and / or apoptotic induction properties.

In addition, the invention further comprises administering the combinations, compositions, formulations, formulations or kits described herein to a patient in need of treatment of a (hyper) proliferative disease and / or disorder, such as cancer, which is responsive to the induction of apoptosis. The present invention relates to a method of treating (hyper) proliferative diseases and / or disorders, such as cancer, which are responsive to the induction of apoptosis.

In addition, the present invention further provides compounds and pharmaceutically acceptable carriers or diluents according to the invention in patients in need of treatment of (hyper) proliferative diseases and / or disorders, such as cancer, of positive or malignant behavior responsive to the induction of apoptosis. Pharmaceutically active, therapeutically effective, and tolerable amounts of pharmaceutical compositions, and pharmaceutically active, therapeutically effective, and tolerable amounts of one or more anticancer agents known in the art, such as one or more of those mentioned herein Treating (excessively) proliferative diseases and / or disorders, such as cancer, of positive or malignant behavior responsive to the induction of apoptosis, including separately, simultaneously, jointly, sequentially or chronologically in combination therapy. It is about how to.

In addition, the present invention also provides for the treatment, prevention or treatment of (hyper) proliferative diseases and / or disorders, such as benign or malignant neoplasms such as cancer, in particular any cancer disease referred to herein, which are responsive to the induction of apoptosis. A predetermined amount of a first active compound which is a compound according to the invention, to a patient in need of improvement, and at least one standard therapeutic agent, in particular at least one anticancer agent known in the art, such as at least one chemotherapy and target mentioned herein Administering a predetermined amount of a second active compound that is a specific anticancer agent separately, simultaneously, jointly, sequentially or chronologically, wherein the amounts of the first active compound and the second active compound cause a therapeutic effect Proliferative diseases and / or disorders reactive to induction of apoptosis, such as benign or malignant neoplasms such as cancer, in particular any of those mentioned herein Treatment of the disease, the present invention relates to a method for the prevention or improvement.

In addition, the invention also relates to (over) proliferative diseases and / or disorders, such as benign or malignant neoplasms, such as cancer, which are responsive to the induction of apoptosis, comprising administering to a patient a combination according to the invention. And, in particular, methods of treating, preventing or ameliorating any cancer disease referred to herein.

In addition, the present invention further provides for the treatment, prevention or amelioration of (hyper) proliferative diseases and / or disorders responsive to the induction of apoptosis, such as cancer, in particular the diseases mentioned herein, eg malignant or benign neoplasms. To a use of a composition, combination, formulation, formulation or kit according to the invention in the manufacture of a pharmaceutical, such as a commercial package or medicament.

The invention further comprises one or more compounds of the invention in combination with instructions for simultaneous, co-, sequential or separate use with one or more chemotherapy and / or target specific anticancer agents such as any of those mentioned herein. Relates to a commercial package.

The present invention further provides one or more of the present invention as the sole active ingredient together with instructions for simultaneous, co-, sequential or separate use with one or more chemotherapy and / or target specific anticancer agents such as any of those mentioned herein. It relates to a commercial package consisting essentially of the compound.

The invention further comprises one or more chemotherapeutic and / or target specific anticancer agents, such as any of those mentioned herein, in combination with instructions for simultaneous, joint, sequential or separate use with one or more compounds according to the invention. Relates to a commercial package.

Compositions, combinations, formulations, formulations, kits or packages referred to in the context of combination therapies according to the invention may also comprise two or more compounds according to the invention and / or two or more of the mentioned anticancer agents known in the art. Can be.

The first and second active ingredients of the combination or parts of the kit according to the invention are subsequently used together for use in combination therapy, staggered simultaneously, jointly, sequentially, separately or chronologically. Provided in dosage form (ie, independently of one another); Or may be packaged and present together as separate components of a combination pack for use in combination therapy, staggered simultaneously, cavities, sequential, separate or chronological.

The types of pharmaceutical formulations of the first and second active ingredients of the combination or parts of the kit according to the invention may be similar, ie both components may be formulated in separate tablets or capsules, or It may be different, i.e. adapted to different dosage forms, for example one active ingredient is formulated in tablets or capsules, and the other may be formulated for intravenous administration, for example.

The amounts of the first and second active ingredients of the combinations, compositions or kits according to the invention are (over) proliferative diseases and / or disorders that are responsive to the induction of apoptosis, in particular one of the diseases mentioned herein, such as malignant or benign. It may together include a therapeutically effective amount for the treatment, prevention or amelioration of neoplasms, especially cancers such as any of the diseases mentioned herein.

In addition, the compounds according to the invention can be used before or after surgical treatment of cancer.

In addition, the compounds of the present invention can also be used in conjunction with radiation therapy.

Combinations according to the invention represent compositions comprising both the compound (s) and other active anticancer agent (s) according to the invention in a fixed combination (fixed unit dosage form), or two or more active ingredients It can represent a medicine pack comprising in separate separate dosage forms (non-fixed combination). In the case of pharmaceutical packs comprising two or more active ingredients, the active ingredients are preferably packaged in blister cards adapted for improved compliance.

Each blister card preferably contains a medicament taken for one day treatment. If the medication is taken at different times of the day, the medication may be placed in different sections on the blister card according to different time ranges of the day the medication is taken (e.g., morning and dinner, or breakfast, lunch and dinner). have. Blister cavities for medications taken together at specific times of the day are administered at each time range of the day. Of course, the various time zones of the day appear on the blister in a clearly visible manner. Of course, it is also possible to indicate the time period over which the medicament should be taken, for example by specifying a time zone.

The daily section can be represented by one line of the blister card, after which the time of day is identified by the chronological sequence of this column.

Medications that must be taken together at certain times of the day are co-located at the appropriate time on the blister card and preferably have the effect of easily pushing them out of the blister and not forgetting to take the dosage form from the blister. Located on a narrow separation distance.

Biological research

ATPase activity of the Eg5 kinesin kinetic domain (Cytoskeleton, class number EG01) can be used to monitor the effect of modulators. Test compounds were dissolved in 10 mM solution in dimethylsulfoxide (DMSO). 2 μl of the appropriate DMSO dilution of the test compound was added to each well of a 96 well flat bottom plate. Each compound dilution was tested three times. Reagents were added and the final reaction of the standard assay was performed in 100 μl of reaction volume in 15 mM Pipes (pH 6.8), 5.0 mM MgCl ₂ , 0.5 mM KCl, 1 mM EGTA, 0.1 mg / ml BSA, 1 μM paclitaxel, 250 nM pre The formed microtubules (cytoskeleton, class number MT001), 300 μM ATP, and Eg5 protein (50 ng) were contained. Controls include buffer wells with ATP and 2% DMSO. The reaction was initiated by addition of ATP, incubated at room temperature for 30 minutes, 20 μl of the reaction volume was taken and added to 80 μl of 1 M perchloric acid followed by the addition of 80 μl of Malachite green reagent. Terminated. Malachit Green Reagent was prepared by mixing a solution of 4.2 g of ammonium molybdate in 100 ml of 4N HCl with a solution of 0.135 g of Malachit Green in 300 ml of H ₂ O. The reaction was incubated for an additional 20 minutes, then read at 615 nm.

The corresponding IC ₅₀ value of the compound for Eg5 inhibition was determined from the concentration-effect curve.

Representative inhibition values measured in the above-mentioned assays [measured by -log IC ₅₀ (mol / L)] are shown in Table A, where the compound number corresponds to the example number.

Antiproliferative / cytotoxic activity of the compounds described herein was determined using Alamar Blue cell viability assays (described in O'Brien et al. Eur J Biochem 267, 5421-5426, 2000). Can be tested on subclones of RKO human colon adenocarcinoma cells (Schmidt et al., Oncogene 19, 2423-2429; 2000). The compound was dissolved in 10 mM solution in DMSO and subsequently diluted in half-log step. DMSO dilutions were further diluted 1: 100 in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum at a final concentration as high as 2 times the final concentration in the test. RKO subclones were seeded in a 96 well flat bottom plate at a concentration of 4000 cells per well in a volume of 50 μl per well. After 24 hours of seeding, 50 μl of each compound dilution in DMEM medium was added to each well of a 96 well plate. Each compound dilution was tested three times. Wells containing untreated control cells were filled with 50 μl of DMEM medium containing 1% DMSO. Cells were then incubated with the material for 72 hours at 37 ° C. in a humid atmosphere containing 5% carbon dioxide. To determine the viability of the cells, 10 μl of Alamar Blue solution (Biosource) was added and the fluorescence was measured at 544 nm absorption and 590 nm emission. To calculate cell viability, the release value from untreated cells was set at 100% viability and the release rate of the treated cells was set for the value of untreated cells. Survival is expressed in% values. The Graphpad Prism program was used for the calculation of EC ₅₀ values for antiproliferative / cytotoxic activity from the dose-response curves obtained.

To determine the specific mode of action of the cell cycle, subclones of RKO colon adenocarcinoma cells (RKOp21 or RKOp27 as described in Schmidt et al. In Oncogene 19, 2423-2429; 2000) were placed in 10 μM in 96 well flat bottom plates. Seeds were seeded at a concentration of 16000 cells per well in a volume of 50 μl per well in DMEM growth medium with 10% FCS containing Forsterone A. After 24 hours of seeding, 50 μl of each compound dilution in DMEM medium was added to each well of a 96 well plate. Each compound dilution was tested three times. Wells containing untreated control cells were filled with 50 μl of DMEM medium containing 1% DMSO. Cells were then incubated with the material for 72 hours at 37 ° C. in a humid atmosphere containing 5% carbon dioxide. To determine the viability of the cells, 10 μl of Alamar Blue solution (biosource) was added and the fluorescence was measured at 544 nm absorption and 590 nm emission. For the calculation of cell viability, the release value from untreated cells was set at 100% viability and the release rate of treated cells was set for the value of untreated cells. Survival is expressed in% values. GraphPad Prism program (GraphPad Software, Inc) was used to calculate EC ₅₀ values from the obtained dose-response curves. The viability of proliferating cells grown in the absence of the inducer, foristeron A, was compared with respect to the survival of cells quiescent by the expression of ectopic p27Kip1 induced by forosterone A.

Representative values for antiproliferative / cytotoxicity measured in the above-mentioned assays [measured with -log EC ₅₀ (mol / L)] are shown in Tables B1, B2 and B3 below, where the compound number is the example number Corresponds to

Induction of apoptosis can be measured using cell death detection ELISA (Roche Biochemicals, Mannheim, Germany). NCI-H460 non-small cell lung cancer cells were seeded in 96 well flat bottom plates at a concentration of 100 cells per well in 50 μl volume of RPMI medium (containing 10% fetal bovine serum) per well. After 24 hours of seeding, 50 μl of each compound dilution in RPMI medium was added to each well of a 96 well plate. Each compound dilution was repeated two or more times. Wells containing untreated control cells were filled with 50 μl of RPMI medium containing 1% DMSO. Cells were then incubated with the material for 24 hours at 37 ° C. in a humid atmosphere containing 5% carbon dioxide. As a positive control for induction of apoptosis, cells were treated with 50 μΜ cisplatin (Gry Pharmaceuticals, Kirch Charten, Germany). The medium was then removed and the cells lysed in 200 μl of lysis buffer. After centrifugation according to the instructions, 10 μl of cell lysates were treated as described in the protocol. The degree of apoptosis was calculated as follows: Absorbance at 405 nm was set to 0.0 cpu, while lysates from cells treated with 50 μM cisplatin and absorbance at 405 nm were obtained at 100 cpu in cisplatin. Setting. The degree of apoptosis was expressed in units of cpu for the value of 100 cpu reached using lysate obtained from cells treated with 50 μM cisplatin.

Experimental variations in Eg5 function lead to characteristic malformations of mitotic spindles, which can be investigated by confocal laser scanning microscopy. HeLa cervical cancer cells were grown overnight in 1800 μl of DMEM medium containing 10% fetal bovine serum on glass cover slips (Nunc® Lab-Tek® Chamber Slides). Test compounds were dissolved in 10 mM solution in DMSO. Appropriate DMSO dilutions of test compounds were further diluted 1:10 in DMEM medium containing 10% fetal bovine serum to a final concentration as high as 10 times the final concentration in the test. After 24 hours of seeding, 200 μl of compound dilution in DMEM medium was added to each well of the cover slip. As a control, 200 μl of DMEM medium containing 10% DMSO was added. After 24 hours of incubation with test compounds, cells were washed with PBS and fixed at 3.7% formaldehyde in H ₂ O at 37 ° C. for 20 minutes. Subsequently, cells were washed with PBS and buffered with 1.471 mM KH ₂ PO ₄ , 8.504 mM Na ₂ HPO ₄ , 137 mM NaCl, 1.325 mM CaCl ₂ , 2.685 mM KCl, 0.542 mM MgCl ₂ (pH 7.2). Incubated with 0.1% Triton X-100 for 15 minutes at room temperature. For saturation of non-specific binding, cells were incubated for 30 minutes at room temperature in 2% BSA / 10% FCS (= blocking buffer) in PBS, followed by anti-alpha tubulin monoclonal antibody (Sigma). , # T5168; 1: 1000) and then incubated with Cy3-conjugated rabbit anti-mouse IgG (H + L) antibody (Jackson Immuno Research; 1: 1000). All antibodies were incubated for 1 hour at 37 ° C. in blocking buffer and cells were washed three times in PBS between each incubation. DNA was counterstained with Hoechst 33342 (0.1 μg / ml). Coverslip mounted on Vectashield (Vector Laboratories, Burlingame, Calif.), And equipped with an appropriate filter Leica TCS SP2 confocal laser scanning microscope (Leica Microsystems ), Bensheim, Germany.

Some compounds according to the invention may be efficacious against p-glycoprotein mediated multidrug-resistant tumor cell lines (eg HCT-15), which can be measured as follows:

All cell lines used were incubated at 37 ° C., 5% CO ₂ and 95% humidity in standard conditions in a tissue culture incubator. On day 1, cells were separated by trypsin / EDTA and pelleted by centrifugation. Cells were resuspended in appropriate concentration in culture medium, seeded in 96 well microtiter plates and incubated overnight at 37 ° C., 5% CO ₂ and 95% humidity in a tissue culture incubator. Stock solutions of all compounds to be tested were dissolved at 10 mM in DMSO and added to microtiter plates of the desired dilution on day 2. The final DMSO concentration of the microtiter plate was maintained at 1%. Control cells were treated only with DMSO. Microtiter plates were incubated with the compound for a further 72 hours at 37 ° C., 5% CO ₂ and 95% humidity in a tissue culture incubator. To measure cell viability on day 5, Alamar Blue solution (BioSource) was added to the microtiter plate in 1/10 culture volume. Cells were incubated for additional 3-6 hours at 37 ° C., 5% CO ₂ and 95% humidity in tissue culture incubators, and fluorescence was measured at 544 nm absorption and 590 nm emission. For the calculation of cell viability, the release value from untreated cells was set at 100% viability and the release rate of treated cells was set against the value of untreated cells. Survival is expressed in% values.

The GraphPad Prism program was used for the calculation of EC ₅₀ values from the obtained dose-response curves.

Claims (23)

Compounds of formula I or salts, stereoisomers or salts of stereoisomers of these compounds: <Formula I>

Where R1 is 1-4C-alkyl, 3-7C-cycloalkyl, 2-4C-alkenyl, 2-4C-alkynyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C substituted with R11 -Alkyl, R11 is -N (R111) R112, or halogen, R111 is hydrogen, 1-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C -Alkyl, 1-4C-alkoxy-2-4C-alkyl, 1N- (1-4C-alkyl) -pyrazolyl, 1N- (H) -pyrazolyl, isoxazolyl, or fully or partially fluorine-substituted 1-4C-alkyl, R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, or 3-7C-cycloalkyl-1-4C-alkyl, R111 and R112 together form the ring Het containing the nitrogen atom to which they are attached, Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thio-morpholine-4 -Yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin- 1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazole-1 -Yl, triazol-1-yl, or tetrazol-1-yl, R113 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkylcarbonyl, amidino, or fully or partially fluorine-substituted 1-4C-alkyl, Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and 1-4C-alkyl, R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl, R 3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy, R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy, R 6 is hydrogen, 1-4C-alkyl or halogen. The method of claim 1, R 1 is 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C-alkyl substituted with R 11, R11 is -N (R111) R112, or halogen, R111 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl Or fully or partially fluorine-substituted 1-4C-alkyl, R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, or 3-7C-cycloalkyl-1-4C-alkyl, or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4- Il, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1 -Yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazol-1-yl, or tetrazol-1-yl, R113 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, 1-4C-alkylcarbonyl, amidino, or fully or partially fluorine-substituted 1-4C-alkyl, Wherein Het may be substituted with 1 or 2 substituents independently selected from fluorine and 1-4C-alkyl, R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl, R3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy, R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy, R 6 is hydrogen, 1-4C-alkyl or halogen Compounds of formula (I) or salts, stereoisomers or salts of stereoisomers of these compounds. The method of claim 1, R 1 is 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, or 2-7C-alkyl substituted with R 11, R11 is -N (R111) R112, R111 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, R112 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, S-oxo-thiomorpholin-4-yl, S, S-dioxo-thiomorpholin-4- 1, pyrrolidin-1-yl, 4N- (R113) -piperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl or triazol-1-yl , R113 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, R 2 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl, 1-4C-alkoxy or hydroxyl, R3 is hydrogen, 1-4C-alkyl, halogen, trifluoromethyl or 1-4C-alkoxy, R 4 is 1-4C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkyl-1-4C-alkyl, R5 is 1-4C-alkyl, halogen, 1-4C-alkoxy, trifluoromethyl, cyano, hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy-2-4C-alkoxy, hydroxy- 2-4C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkyl-1-4C-alkoxy, or fully or predominantly fluorine-substituted 1-4C-alkoxy, R 6 is hydrogen, 1-4C-alkyl or halogen Compounds of formula (I) or salts, stereoisomers or salts of stereoisomers of these compounds. The compound according to any one of claims 1 to 3, or a salt thereof, having a coordination represented by the following formula (I *) for positions 3a and 10: <Formula I *>

The method according to any one of claims 1, 2 and 4, R 1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclopropylmethyl, ethyl substituted with R 11, propyl substituted with R 11, or butyl substituted with R 11, R11 is -N (R111) R112, fluorine, chlorine or bromine, R111 is hydrogen, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoro Ethyl, or 2,2,2-trifluoroethyl, R112 is methyl or or R111 is ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, R112 is ethyl, isopropyl, or cyclopropyl, or or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N -(R113) -piperazin-1-yl, 4N- (R113) -homopiperazin-1-yl, pyrrole-1-yl, pyrazol-1-yl, imidazol-1-yl, triazole-1 -Yl, or tetrazol-1-yl, R113 is hydrogen, methyl, ethyl, propyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, Wherein Het may be substituted with one or two substituents independently selected from fluorine and methyl, R2 is hydrogen, R3 is hydrogen, R 4 is methyl, ethyl, propyl, isopropyl, cyclopropyl or cyclopropylmethyl, R 5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropyloxy, cyclopropylmethoxy, or fully or predominantly Fluorine-substituted 1-2C-alkoxy, R6 is hydrogen, Where R5 binds to the 6-position of the skeleton Compounds of formula (I) or salts, stereoisomers or salts of stereoisomers of these compounds. The method of claim 1, R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl, R11 is -N (R111) R112, R111 is hydrogen, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-meth Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoethyl, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, tertbutyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-meth Methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, R112 is methyl or or R111 is ethyl, propyl, isopropyl, allyl, propargyl, 1-methyl-propargyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl , 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, R112 is ethyl or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, homopiperidin-1-yl, 4N- (R113) -piperazin- 1-yl, 4N- (R113) -homopiperazin-1-yl, 2,5-dihydro-pyrrole-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, 4-methyl -Piperidin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoropiperidin-1-yl, (S) -3-fluoro-pyrrolidine- 1-yl, (R) -3-fluoro-pyrrolidin-1-yl, or 3,3-difluoro-pyrrolidin-1-yl, R113 is methyl or acetyl, or or Het is pyrazol-1-yl, or imidazol-1-yl, R2 is hydrogen, R3 is hydrogen, R 4 is methyl, R5 is chlorine, bromine, fluorine, ethoxy, methoxy, difluoromethoxy or trifluoromethoxy, R6 is hydrogen or fluorine Where R5 binds to the 6-position of the skeleton, R6 binds to the 5- or 7-position of the skeleton Compounds of formula (I *) or salts of these compounds as defined in claim 4. The method of claim 1, R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl, R11 is -N (R111) R112, R 111 is methyl, ethyl, isopropyl, isobutyl, tertbutyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl, R112 is hydrogen, or R 111 is methyl, ethyl, isopropyl, allyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, or 2-methoxyethyl, R112 is methyl or or R 111 is ethyl, 2-hydroxyethyl, or 2-methoxyethyl, R112 is ethyl or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, pyrrolidin-1-yl, azetidin-1-yl, 2,5-dihydro-pyrrole-1-yl, or 1,2,3,6-tetrahydropyridine -1- days, R2 is hydrogen, R3 is hydrogen, R 4 is methyl, R5 is chlorine, bromine, ethoxy, methoxy or difluoromethoxy, R6 is hydrogen or fluorine Where R5 binds to the 6-position of the skeleton, R6 binds to the 7-position of the skeleton Compounds of formula (I *) or salts of these compounds as defined in claim 4. The method according to claim 1 or 2, R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl, R11 is -N (R111) R112, R111 is hydrogen, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl, R112 is hydrogen, or R111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl Or 2,2,2-trifluoroethyl, R112 is methyl or or R111 is ethyl, propyl, isopropyl, cyclopropyl, 2-hydroxyethyl, 2-methoxyethyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl ego, R112 is ethyl or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, or 4N- (R113) -piperazin-1-yl, R113 is hydrogen, methyl, ethyl, isopropyl, acetyl, 2-fluoroethyl, 2,2-difluoroethyl, or 2,2,2-trifluoroethyl, Wherein Het may be substituted with one or two substituents independently selected from fluorine and methyl, or or Het is pyrazol-1-yl, imidazol-1-yl, or triazol-1-yl, R2 is hydrogen, R3 is hydrogen, R 4 is methyl, ethyl, isopropyl or cyclopropyl, R5 is chlorine, bromine, fluorine, ethoxy, methoxy, propoxy, isopropoxy, cyclopropylmethoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy, R6 is hydrogen, Where R5 binds to the 6-position of the skeleton Compounds of formula (I *) or salts of these compounds as defined in claim 4. The method according to claim 1 or 2, R 1 is 2- (R 11) -ethyl, or 3- (R 11) -propyl, R11 is -N (R111) R112, R111 is hydrogen, R112 is hydrogen, or R 111 is methyl, ethyl, propyl, isopropyl, isobutyl, cyclopropyl, cyclobutyl, or cyclopropylmethyl, R112 is hydrogen, or R 111 is methyl, ethyl, isopropyl, or cyclopropyl, R112 is methyl or or R111 is ethyl, isopropyl, or cyclopropyl, R112 is ethyl or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, azetidin-1-yl, 4N- (R113) -piperazin-1-yl, 4-methyl-pi Ferridin-1-yl, 4-fluoro-piperidin-1-yl, 4,4-difluoropiperidin-1-yl, (S) -3-fluoro-pyrrolidine-1- 1, (R) -3-fluoro-pyrrolidin-1-yl, 3,3-difluoro-pyrrolidin-1-yl, 3-fluoro-azetidin-1-yl, or 3, 3-difluoro-azetidin-1-yl, R113 is hydrogen, methyl, or acetyl, or or Het is pyrazol-1-yl, or imidazol-1-yl, R2 is hydrogen, R3 is hydrogen, R 4 is methyl or ethyl, R5 is chlorine, bromine, fluorine, ethoxy, methoxy, or fully or predominantly fluorine-substituted 1-2C-alkoxy, R6 is hydrogen, Where R5 binds to the 6-position of the skeleton Compounds of formula (I *) or salts of these compounds as defined in claim 4. The method according to any one of claims 1 to 3, R 1 is methyl, 2- (R 11) -ethyl, or 3- (R 11) -propyl, R11 is -N (R111) R112, R111 is methyl R112 is methyl or or R111 and R112 together comprise the nitrogen atom to which they are attached to form a ring Het, Het is piperidin-1-yl, morpholin-4-yl, pyrrolidin-1-yl, 4-methyl-piperazin-1-yl, pyrazol-1-yl, imidazol-1-yl or Triazol-1-yl, R2 is hydrogen, R3 is hydrogen, R 4 is methyl, ethyl, isopropyl or cyclopropyl, R5 is methyl, fluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethyl, 2-methoxy-ethoxy, cyclopropylmethoxy, difluoromethoxy or trifluoromethoxy ego, R6 is hydrogen, Where R5 binds to the 6-position of the skeleton Compounds of formula (I *) or salts of these compounds as defined in claim 4. The compound of claim 1, wherein the compound of any one of formulas Ia *, Ib * and Ic * or salts of these compounds: <Formula Ia *>

<Formula Ib *>

<Formula Ic *>

Where R2 and R3 are both hydrogen, R 4 is methyl or ethyl, R1 and R5 have the meaning of any one of 1.1 to 1.891 below.

<Claim 11> The method of claim 1, 1. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione 2. (3aS, 10R) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 3. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione 4. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza- Cyclopenta [b] fluorene-1,3-dione 5. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclo Penta [b] fluorene-1,3-dione 6. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6- (2-methoxy-ethoxy) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 7. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 8. (3aS, 10R) -6-Bromo-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 9. (3aS, 10R) -6-Chloro-2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 10. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 11. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 12. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 13. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 14. (3aS, 10R) -2- (4-Dimethylamino-butyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 15. (3aS, 10R) -2- (3-Dimethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 16. (3aS, 10R) -6-chloro-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 17. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 18. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 19. (3aS, 10R) -2- (3-Dimethylamino-propyl) -3a-ethyl-10- (3-hydroxy-phenyl) -6-methoxy-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 20. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-imidazol-1-yl-propyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 21. (3aS, 10R) -6-cyclopropylmethoxy-10- (3-hydroxy-phenyl) -2,3a-dimethyl-3a, 4,9,10-tetrahydro-2,9,10a-tree Aza-cyclopenta [b] fluorene-1,3-dione 22. (3aS, 10R) -2- (2-Bromo-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 23. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 24. (3aS, 10R) -2- (2-Bromo-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 25. (3aS, 10R) -2- (2-Amino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 26. (3aS, 10R) -2- (2-Bromo-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 27. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 28. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 29. (3aS, 10R) -2- (2-Azetidin-1-yl-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 30. (3aS, 10R) -2- (2-Amino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 31. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-imidazol-1-yl-ethyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 32. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 33. (3aS, 10R) -2- (2-azetidin-1-yl-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 34. (3aS, 10R) -2- [2- (3,3-Difluoro-pyrrolidin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 35. (3aS, 10R) -2- (2-Ethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 36. (3aS, 10R) -2- (2-Bromo-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 37. (3aS, 10R) -6-Chloro-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 38. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 39. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 40. (3aS, 10R) -6-Chloro-2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 41. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 42. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 43. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (2-dimethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 44. (3aS, 10R) -2- (2-Azetidin-1-yl-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 45. (3aS, 10R) -2- (2-Amino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 46. (3aS, 10R) -2- (2-azetidin-1-yl-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 47. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 48. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 49. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 50. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 51. (3aS, 10R) -2- (3-Ethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 52. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione, 53. (3aS, 10R) -2- (2-cyclopropylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione, 54. (3aS, 10R) -6-Bromo-2- (2-bromo-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 55. (3aS, 10R) -2- (3-Chloro-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 56. (3aS, 10R) -2- (3-Chloro-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 57. (3aS, 10R) -6-Chloro-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2, 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 58. (3aS, 10R) -6-Bromo-2- (3-chloro-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 59. (3aS, 10R) -2- (3-Chloro-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 60. (3aS, 10R) -2- (2-Bromo-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 61. (3aS, 10R) -2- (2-Bromo-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 62. (3aS, 10R) -2- (2-Bromo-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 63. (3aS, 10R) -2- (3-Chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 64. (3aS, 10R) -6-Chloro-2- (3-chloro-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 65. (3aS, 10R) -2- (3-Chloro-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 66. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -6-hydroxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 67. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 68. (3aS, 10R) -2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 69. (3aS, 10R) -2- (2-Diethylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 70. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 71. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 72. (3aS, 10R) -2- (2-tert-butylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 73. (3aS, 10R) -2- [2- (2,2-Difluoro-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 74. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 75. (3aS, 10R) -10- (3-Hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 76. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 77. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 78. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 79. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 80. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 81. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 82. (3aS, 10R) -2- [2- (2-Hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 83. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 84. (3aS, 10R) -2- (2-allylamino-ethyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 85. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 86. (3aS, 10R) -2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 87. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 88. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 89. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 90. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 91. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (1-methyl-1H-pyrazol-3-ylamino) -ethyl ] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 92. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 93. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 94. (3aS, 10R) -10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 95. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 96. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 97. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 98. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 99. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 100. (3aS, 10R) -6-Chloro-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a- Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 101. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 102. (3aS, 10R) -6-Chloro-2- (2-cyclopropylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 103. (3aS, 10R) -6-Chloro-2- (2-cyclobutylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 104. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 105. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 106. (3aS, 10R) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 107. (3aS, 10R) -2- (3-Diethylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 108. (3aS, 10R) -6-Chloro-2- [2- (cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 109. (3aS, 10R) -6-Chloro-2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 110. (3aS, 10R) -6-Chloro-2- (2-diethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 111. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 112. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 113. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 114. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 115. (3aS, 10R) -2- (2-allylamino-ethyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 116. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 117. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 118. (3aS, 10R) -2- {2-[(2-Hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 119. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 120. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 121. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 122. (3aS, 10R) -6-Chloro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 123. (3aS, 10R) -6-Chloro-2- [2- (2,2-difluoro-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 124. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 125. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (1-methyl-1H-pyrazol-3-ylamino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 126. (3aS, 10R) -6-Chloro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 127. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 128. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 129. (3aS, 10R) -6-Chloro-2- [2- (3,3-difluoro-pyrrolidin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 130. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 131. (3aS, 10R) -6-Chloro-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 132. (3aS, 10R) -6-Chloro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 133. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 134. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (2-methyl-2H-pyrazol-3-ylamino) -ethyl ] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 135. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 136. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3-((R and S) 1-methyl-prop-2-ynylamino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 137. (3aS, 10R) -6-Chloro-2- (3-diethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 138. (3aS, 10R) -6-Chloro-2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 139. (3aS, 10R) -2- (3-allylamino-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2 , 9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 140. (3aS, 10R) -6-Chloro-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 141. (3aS, 10R) -2- (3-azetidin-1-yl-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 142. (3aS, 10R) -2- [3- (2,2-Difluoro-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 143. (3aS, 10R) -2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 144. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 145. (3aS, 10R) -2- [3- (2-Hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 146. (3aS, 10R) -2- (3-allylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 147. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 148. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 149. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 150. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 151. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 152. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 153. (3aS, 10R) -6-ethoxy-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 154. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 155. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 156. (3aS, 10R) -2- (2-tert-butylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 157. (3aS, 10R) -2- (2-allylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 158. (3aS, 10R) -6-Ethoxy-2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 159. (3aS, 10R) -6-Ethoxy-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 160. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 161. (3aS, 10R) -2- (2-cyclopropylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 162. (3aS, 10R) -2- (2-diethylamino-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 163. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 164. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 165. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 166. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 167. (3aS, 10R) -2- (3-tert-butylamino-propyl) -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 168. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 169. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 170. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 171. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 172. (3aS, 10R) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 173. (3aS, 10R) -6-Chloro-2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 174. (3aS, 10R) -6-Chloro-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a- Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 175. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 176. (3aS, 10R) -2- (3-Diethylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 177. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 178. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 179. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 180. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10- Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 181. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 182. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 183. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2 -Inyl-amino) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 184. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 185. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 186. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 187. (3aS, 10R) -6-Ethoxy-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 188. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 189. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 190. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 191. (3aS, 10R) -2- (3-allylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 192. (3aS, 10R) -6-Ethoxy-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 193. (3aS, 10R) -6-Ethoxy-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 194. (3aS, 10R) -6-Ethoxy-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 195. (3aS, 10R) -6-Ethoxy-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 196. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 197. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 198. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 199. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 200. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 201. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl ) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 202. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 203. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 204. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 205. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl ] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 206. (3aS, 10R) -2- (3-allylamino-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 207. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 208. (3aS, 10R) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 209. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 210. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 211. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 212. (3aS, 10R) -6-Bromo-2- (3-ethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 213. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 214. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 215. (3aS, 10R) -6-Bromo-2- (3-cyclopropylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 216. (3aS, 10R) -6-Bromo-2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 217. (3aS, 10R) -6-Bromo-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 218. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 219. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 220. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 221. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 222. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 223. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 224. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 225. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 226. (3aS, 10R) -2- (3-Dimethylamino-propyl) -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 227. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 228. (3aS, 10R) -6-Bromo-2- (3-diethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 229. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 230. (3aS, 10R) -6-Bromo-2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 231. (3aS, 10R) -6-Bromo-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 232. (3aS, 10R) -6-Bromo-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 233. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 234. (3aS, 10R) -6-Bromo-2- [3- (cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 235. (3aS, 10R) -6-Bromo-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 236. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl- Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 237. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl -Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 238. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 239. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl -Propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 240. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazine -1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 241. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6- (1,1-difluoro-methoxy) -10- (3-hydric Oxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 242. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 243. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 244. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperi Din-1-yl) -propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 245. (3aS, 10R) -7-Fluoro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 246. (3aS, 10R) -7-Fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 247. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [3- (ethyl-methyl-amino) -propyl] -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 248. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 249. (3aS, 10R) -2- (2-Ethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 250. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 251. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 252. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 253. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 254. (3aS, 10R) -2- (2-allylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 255. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 256. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 257. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 258. (3aS, 10R) -2- (2-Diethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 259. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 260. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 261. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 262. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 263. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 264. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl ) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 265. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 266. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 267. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 268. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 269. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 270. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 271. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl ] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 272. (3aS, 10R) -2- (2-Cyclobutylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 273. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 274. (3aS, 10R) -2- (2-allylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 275. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (ethyl-methyl-amino) -ethyl] -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 276. (3aS, 10R) -2- (2-Diethylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 277. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 278. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 279. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 280. (3aS, 10R) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 281. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 282. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 283. (3aS, 10R) -2- (2-Amino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 284. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 285. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl ) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 286. (3aS, 10R) -2- (2-Cyclopropylamino-ethyl) -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 287. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-prop-2-ynylamino -Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 288. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 289. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 290. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydroxy-phenyl)- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 291. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2 -Inyl-amino) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 292. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl- Ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 293. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperi Din-1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 294. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazine -1-yl) -ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 295. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6- (1,1-difluoro-methoxy) -10- (3-hydric Oxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 296. (3aS, 10R) -6-Ethoxy-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 297. (3aS, 10R) -6-Ethoxy-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 298. (3aS, 10R) -6-Ethoxy-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 299. (3aS, 10R) -6-Ethoxy-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 300. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 301. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 302. (3aS, 10R) -6-Ethoxy-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 303. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 304. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 305. (3aS, 10R) -7-Fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 306. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 307. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 308. (3aS, 10R) -2- (3-tert-Butylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 309. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 310. (3aS, 10R) -2- (3-Dimethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 311. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 312. (3aS, 10R) -7-Fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 313. (3aS, 10R) -2- (3-Diethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 314. (3aS, 10R) -6- (1,1-difluoro-methoxy) -2- (3-dimethylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 315. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 316. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 317. (3aS, 10R) -2- [3- (Allyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 318. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 319. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 320. (3aS, 10R) -2- (3-Azetidin-1-yl-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 321. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 322. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 323. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 324. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 325. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 326. (3aS, 10R) -2- [3- (3,6-Dihydro-2H-pyridin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 327. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl ) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 328. (3aS, 10R) -2- [3- (4-Acetyl-piperazin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 329. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 330. (3aS, 10R) -2- (3-Ethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 331. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 332. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 333. (3aS, 10R) -2- (3-Cyclobutylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 334. (3aS, 10R) -2- (3-allylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 335. (3aS, 10R) -6-Chloro-2- (3-dimethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 336. (3aS, 10R) -6-Chloro-2- (2-diethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 337. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 338. (3aS, 10R) -6-Chloro-2- (2-ethylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 339. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 340. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 341. (3aS, 10R) -6-Chloro-2- [2- (cyclopropylmethyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 342. (3aS, 10R) -6-Chloro-7-fluoro-2- [2- (2-hydroxy-ethylamino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 343. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 344. (3aS, 10R) -6-Chloro-2- (2-cyclobutylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 345. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 346. (3aS, 10R) -2- (2-allylamino-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 347. (3aS, 10R) -6-Chloro-2- [2- (ethyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 348. (3aS, 10R) -6-Chloro-7-fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 349. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 350. (3aS, 10R) -6-Chloro-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 351. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino)- Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 352. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 353. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 354. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 355. (3aS, 10R) -6-Chloro-2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 356. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 357. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 358. (3aS, 10R) -6-Chloro-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -7-fluoro-10- (3-hydroxy- Phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 359. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl)- Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 360. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 361. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 362. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 363. (3aS, 10R) -2- (3-allylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 364. (3aS, 10R) -2- [3- (Ethyl-methyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 365. (3aS, 10R) -2- {3- [Ethyl- (2-methoxy-ethyl) -amino] -propyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 366. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-piperidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 367. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperidin-1-yl ) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 368. (3aS, 10R) -2- [3- (3,6-Dihydro-2H-pyridin-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 369. (3aS, 10R) -6-Bromo-2- (3-cyclobutylamino-propyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 370. (3aS, 10R) -6-Bromo-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 371. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 372. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 373. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 374. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 375. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -propyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 376. (3aS, 10R) -6-Bromo-2- [2- (cyclopropylmethyl-amino) -ethyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 377. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 378. (3aS, 10R) -6-Bromo-2- (2-tert-butylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetra Hydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 379. (3aS, 10R) -6-Bromo-2- {2- [ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 380. (3aS, 10R) -6-Bromo-2- {2- [ethyl- (2-methoxy-ethyl) -amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 381. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 382. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 383. (3aS, 10R) -2- (2-allylamino-ethyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 384. (3aS, 10R) -6-Bromo-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 385. (3aS, 10R) -6-Bromo-2- (2-diethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 386. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -ethyl] -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 387. (3aS, 10R) -2- [2- (4-acetyl-piperazin-1-yl) -ethyl] -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 388. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-morpholin-4-yl-ethyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 389. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 390. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 391. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 392. (3aS, 10R) -6-Chloro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 393. (3aS, 10R) -6-Bromo-2- (2-ethylamino-ethyl) -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 394. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9,10-tetrahydro- 2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 395. (3aS, 10R) -6-Bromo-2- [2- (3,6-dihydro-2H-pyridin-1-yl) -ethyl] -10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 396. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -6-bromo-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 397. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 398. (3aS, 10R) -2- (2-Azepan-1-yl-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 399. (3aS, 10R) -2- [2- (4-Acetyl-piperazin-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 400. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperazin-1-yl) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 401. (3aS, 10R) -2- [2- (3,6-Dihydro-2H-pyridin-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6 -Methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 402. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (4-methyl-piperidin-1-yl ) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 403. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-piperidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 404. (3aS, 10R) -2- [2- (2,5-dihydro-pyrrol-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 405. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-pyrrolidin-1-yl-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 406. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-methylamino-ethyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 407. (3aS, 10R) -2- (2-Ethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 408. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isopropylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 409. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (2-isobutylamino-ethyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 410. (3aS, 10R) -2- [2- (Cyclopropylmethyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 411. (3aS, 10R) -2- [2- (2,5-Dihydro-pyrrole-1-yl) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 412. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [2- (2-methoxy-ethylamino) -ethyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 413. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 414. (3aS, 10R) -2- (2-tert-Butylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 415. (3aS, 10R) -2- (2-allylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 416. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (2-prop-2-ynylamino-ethyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 417. (3aS, 10R) -2- (2-Dimethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 418. (3aS, 10R) -2- [2- (Ethyl-methyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 419. (3aS, 10R) -5-Fluoro-2- {2-[(2-hydroxy-ethyl) -methyl-amino] -ethyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 420. (3aS, 10R) -2- (2-Diethylamino-ethyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 421. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 422. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 423. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 424. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 425. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 426. (3aS, 10R) -2- (2-cyclobutylamino-ethyl) -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 427. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-methylamino-propyl) -3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 428. (3aS, 10R) -2- (3-Ethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 429. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 430. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 431. (3aS, 10R) -2- [3- (Cyclopropylmethyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 432. (3aS, 10R) -5-Fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 433. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 434. (3aS, 10R) -2- (3-Cyclopropylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 435. (3aS, 10R) -2- (3-cyclobutylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 436. (3aS, 10R) -2- (3-tert-Butylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 437. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 438. (3aS, 10R) -2- (3-Dimethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 439. (3aS, 10R) -5-Fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 440. (3aS, 10R) -2- (3-Diethylamino-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 441. (3aS, 10R) -2- {3- [Ethyl- (2-hydroxy-ethyl) -amino] -propyl} -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 442. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 443. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (methyl-prop-2-ynyl-amino) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 444. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -6-methoxy-3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 445. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 446. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 447. (3aS, 10R) -2- [3- (2,5-Dihydro-pyrrole-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 448. (3aS, 10R) -5-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [3- (4-methyl-piperazin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 449. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy- 3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 450. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -5-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 451. (3aS, 10R) -2- {2- [Ethyl- (2-hydroxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 452. (3aS, 10R) -2- [2- (Allyl-methyl-amino) -ethyl] -7-fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 453. (3aS, 10R) -6- (1,1-Difluoro-methoxy) -2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3 -Hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 454. (3aS, 10R) -2- {2- [Ethyl- (2-methoxy-ethyl) -amino] -ethyl} -7-fluoro-10- (3-hydroxy-phenyl) -6-meth Oxy-3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 455. (3aS, 10R) -7-Fluoro-10- (3-hydroxy-phenyl) -6-methoxy-3a-methyl-2- [2- (methyl-prop-2-ynyl-amino) -Ethyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 456. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-methylamino-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 457. (3aS, 10R) -6-Chloro-2- (3-ethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 458. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (3-isopropylamino-propyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 459. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- (3-isobutylamino-propyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 460. (3aS, 10R) -6-Chloro-2- [3- (cyclopropylmethyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 461. (3aS, 10R) -6-Chloro-7-fluoro-2- [3- (2-hydroxy-ethylamino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 462. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 463. (3aS, 10R) -6-Chloro-2- (3-cyclobutylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 464. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 465. (3aS, 10R) -2- (3-allylamino-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 466. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-prop-2-ynylamino-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 467. (3aS, 10R) -6-Chloro-2- [3- (ethyl-methyl-amino) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 468. (3aS, 10R) -6-Chloro-7-fluoro-2- {3-[(2-hydroxy-ethyl) -methyl-amino] -propyl} -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 469. (3aS, 10R) -6-Chloro-2- (3-diethylamino-propyl) -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9, 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 470. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-hydroxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 471. (3aS, 10R) -6-Chloro-2- {3- [ethyl- (2-methoxy-ethyl) -amino] -propyl} -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 472. (3aS, 10R) -2- [3- (allyl-methyl-amino) -propyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 473. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (methyl-prop-2-ynyl-amino)- Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 474. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -2- [3- (isopropyl-methyl-amino) -propyl] -3a-methyl-3a , 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 475. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 476. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-pyrrolidin-1-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 477. (3aS, 10R) -6-Chloro-2- [3- (2,5-dihydro-pyrrol-1-yl) -propyl] -7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 478. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-piperidin-1-yl-propyl) -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 479. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 480. (3aS, 10R) -6-Chloro-2- [3- (3,6-dihydro-2H-pyridin-1-yl) -propyl] -7-fluoro-10- (3-hydroxy- Phenyl) -3a-methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 481. (3aS, 10R) -6-Chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperazin-1-yl)- Propyl] -3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 482. (3aS, 10R) -2- [3- (4-acetyl-piperazin-1-yl) -propyl] -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a -Methyl-3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 483. (3aS, 10R) -2- (3-Azepan-1-yl-propyl) -6-chloro-7-fluoro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4 , 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 484. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- (3-morpholin-4-yl-propyl) -3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 485. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [3- (4-methyl-piperidin-1-yl) -propyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 486. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -2- [2- (isopropyl-methyl-amino) -ethyl] -3a-methyl-3a, 4,9 , 10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 487. (3aS, 10R) -6-Bromo-10- (3-hydroxy-phenyl) -3a-methyl-2- [2- (4-methyl-piperidin-1-yl) -ethyl]- 3a, 4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 488. (3aS, 10R) -6-Chloro-2- [3- (cyclopropylmethyl-amino) -propyl] -10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10 Tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione 489. (3aS, 10R) -2- (3-tert-butylamino-propyl) -6-chloro-10- (3-hydroxy-phenyl) -3a-methyl-3a, 4,9,10-tetrahydro -2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione and 490. (3aS, 10R) -10- (3-hydroxy-phenyl) -6-methoxy-2- [3- (2-methoxy-ethylamino) -propyl] -3a-methyl-3a, 4, 9,10-tetrahydro-2,9,10a-triaza-cyclopenta [b] fluorene-1,3-dione Compounds of formula (I) or salts thereof selected from The method according to any one of claims 1 to 11, R 1 is 2- (R 11) -ethyl or 3- (R 11) -propyl; R2 and R3 are both hydrogen; R 4 is methyl; R 5 is bonded at the 6-position of the skeleton and is chlorine, bromine, ethoxy, methoxy or difluoromethoxy; At least one of R 6 is hydrogen Compounds or salts, stereoisomers or salts of stereoisomers of these compounds. The method according to any one of claims 1 to 12, R 1 is 2- (R 11) -ethyl; R2 and R3 are both hydrogen; R 4 is methyl; R 5 is bonded at the 6-position of the skeleton and is chlorine, ethoxy, methoxy or difluoromethoxy; At least one of R 6 is hydrogen Compounds or salts, stereoisomers or salts of stereoisomers of these compounds. 14. A compound according to any one of claims 1 to 13 for use in the treatment of a disease. A pharmaceutical composition comprising at least one compound according to claim 1 and conventional pharmaceutical auxiliaries and / or excipients. The method according to claims 1 to 13 in the manufacture of a pharmaceutical composition for the treatment of (hyper) proliferative diseases and / or disorders reactive to induction of apoptosis, including benign and / or malignant neoplasms and / or cancers. Use of a compound according to claim 1. A therapeutically effective and tolerable amount of at least one compound according to any one of claims 1 to 13 is excessive (responsive to induction of apoptosis, including benign or malignant neoplasms and / or cancers). A method of treating, preventing or ameliorating said disease and / or disorder in said mammal, comprising administering to said mammal in need of treating, preventing or ameliorating a proliferative disease and / or disorder. A method of modulating Eg5 kinesin activity, comprising administering to a mammal in need thereof a therapeutically effective and tolerable amount of at least one compound according to any one of claims 1 to 13. A first active ingredient which is at least one compound according to any one of claims 1 to 13, and A second active ingredient comprising at least one anticancer agent selected from the group consisting of a chemotherapeutic anticancer agent and a target-specific anticancer agent, Separately, sequentially, concurrently with therapies, including therapies of (over) proliferative diseases and / or disorders of positive or malignant behavior responsive to the induction of apoptosis, including benign and / or malignant neoplasms and / or cancers, Combinations for use jointly or chronologically staggered. A predetermined amount of a first active ingredient which is a compound according to any one of claims 1 to 13, and A predetermined amount of at least one second active ingredient which is an anticancer agent selected from the group consisting of a chemotherapeutic anticancer agent and a target-specific anticancer agent Parallax separately, sequentially, simultaneously, jointly or chronologically for patients in need of treating, preventing or ameliorating hyperproliferative diseases and / or disorders responsive to the induction of apoptosis, including benign or malignant neoplasms and / or cancers. Including administering Wherein the amounts of the first active compound and the second active compound cause a therapeutic effect, A method of treating, preventing or ameliorating said disease and / or disorder in said patient. 21. The method according to claim 19 or 20, wherein the chemotherapy anticancer agent comprises (i) Cyclophosphamid, Ifosfamid, Thiotepa, Melphalan and Chloroethylnitrosourea. Alkylating agent / carbamylating agent comprising; (ii) platinum derivatives including cisplatin, oxaliplatin, satraplatin and carboplatin; (iii) taxanes, including vinca alkaloids such as vincristine, vinblastine or vinorelbine, paclitaxel, docetaxel and analogs, as well as formulations and conjugates thereof comprising abraxane, and epothilones Mitosis inhibitors / tubulin inhibitors including epothilones including Epothilone B, Azaepothilone or ZK-EPO; (iv) camptothecins and camptothecin analogs, including anthracyclines, including doxorubicin, epipodophyllotoxins, including etoposide, and irinotecan or topotecan Topoisomerase inhibitors; (v) pyrimidine antagonists including 5-fluorouracil, Capecitabine, Arabinosylcytosine / Cytarabin and Gemcitabine; (vi) purine antagonists including 6-mercaptopurine, 6-thioguanine and fludarabine; And (vii) a folic acid antagonist comprising methotrexate and pemetrexed. The method of claim 19, wherein the target-specific anticancer agent is selected from (i) Imatinib, ZD-1839 / Gefitinib, BAY43-9006 / Sorafenib ( Sorafenib, SU11248 / Sunitinib, OSI-774 / Erlotinib, Dasatinib, Lapatinib, Batalanib, Vandeanib And kinase inhibitors including Pazopanib; (ii) proteasome inhibitors including PS-341 / Bortezomib; (iii) histone deacetyl, including SAHA, PXD101, MS275, MGCD0103, Depsipeptide / FK228, NVP-LBH589, NVP-LAQ824, Valproic Acid (VPA), CRA / PCI 24781, ITF2357, SB939 and Butyrate Lase inhibitors; (iv) heat shock protein 90 inhibitor comprising 17-allylaminogeldanamycin (17-AAG) and 17-dimethylaminogeldanamycin (17-DMAG); (v) vascular targeting agents (VAT), including combretastatin A4 phosphate and AVE8062 / AC7700, and VEGF antibodies such as Bevacizumab and PTK787 / ZK222584 (Vatalanib), vandetanib Antiangiogenic drugs, including KDR tyrosine kinase inhibitors such as Vandanib or Pazopanib; (vi) Trastuzumab, Rituximab, Alemtuzumab, Tositumomab, Cetuximab, Bevacizumab and Panituzumab Monoclonal antibodies, including Panitumumab), as well as mutants and conjugates of monoclonal antibodies, such as Gemtuzumab ozogamicin or Ibritumomab tiuxetan and antibody fragments; (vii) oligonucleotide-based therapeutics, including G-3139 / Oblimersen and DNMT1 inhibitor MG98; (viii) Toll-like receptor / TLR 9 agonists, including Promune®, TLR 7 agonists and analogs thereof, including imiquimod and isatoribine Immunostimulatory RNAs as TLR 7/8 agonists as well as TLR 7/8 agonists including Resiquimod; (ix) protease inhibitors; (x) antiestrogens such as tamoxifen or raloxifene, antiandrogens such as flutamide or casodex, LHRH analogues such as lupolide Hormonal therapeutics, including Goserelin or Triptorelin, and aromatase inhibitors; Bleomycin; Retinoids including all-trans retinoic acid (ATRA); DNA methyltransferase inhibitors including 2-deoxycytidine derivative decitabine and 5-azacytidine; Alanosine; Cytokines including interleukin-2; Interferons, including interferon a2 and interferon-γ; And death receptor agonists, including TRAIL, DR4 / 5 agonist antibodies, FasL and TNF-R agonists such as TRAIL receptor agonists like mapatumumab or lexatumumab. Combination or method. 21. The method of any one of claims 16, 17, 19 and 20, wherein the cancer is Breast, bladder, bone, brain, central and peripheral nervous system, colon, endocrine glands, esophagus, endometrium, germ cell, head and neck, kidney, liver, lung, larynx and hypopharynx, mesothelioma, sarcoma, ovary, pancreas, prostate, Cancer of the rectum, kidney, small intestine, soft tissue, testes, stomach, skin, ureters, vagina and vulva; Hereditary cancer, retinoblastoma and Wilms' tumor; Leukemia, lymphoma, non-Hodgkin's disease, chronic and acute myeloid leukemia, acute lymphoblastic leukemia, Hodgkin's disease, multiple myeloma and T-cell lymphoma; Myelodysplastic syndrome, plasma cell neoplasia, paraneoplastic syndrome, cancer of unknown primary site and malignant tumor related to AIDS Use, method or combination selected from the group consisting of.